Trial Outcomes & Findings for Established Status Epilepticus Treatment Trial (NCT NCT01960075)

NCT ID: NCT01960075

Last Updated: 2021-06-14

Results Overview

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 478 participants
• Primary outcome timeframe: Within 60 minutes after the start of study drug infusion
• Results posted on: 2021-06-14

Participant Flow

ESETT had a total of 478 enrollments. This number includes 16 re-enrollers. This was an EFIC trial so all consents happened after treatment. All enrollments went through the same process of consent even if they were reenrolled. The first 400 patients were used in several parts of analyses since the trial stopped early for futility (prespecified).

Participant milestones

Measure	Fosphenytoin (FOS) Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Overall Study STARTED	149	149	180
Overall Study COMPLETED	141	146	173
Overall Study NOT COMPLETED	8	3	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Established Status Epilepticus Treatment Trial

Baseline characteristics by cohort

Measure	Fosphenytoin (FOS) n=118 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=121 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=145 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam	Total n=384 Participants Total of all reporting groups
Age, Continuous	32.8 years STANDARD_DEVIATION 25.4 • n=5 Participants	32.2 years STANDARD_DEVIATION 25.4 • n=7 Participants	33.3 years STANDARD_DEVIATION 26.0 • n=5 Participants	32.8 years STANDARD_DEVIATION 25.6 • n=4 Participants
Age, Customized Age · 0 - 5 yr	24 Participants n=5 Participants	28 Participants n=7 Participants	30 Participants n=5 Participants	82 Participants n=4 Participants
Age, Customized Age · 6 - 10 yr	15 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants	39 Participants n=4 Participants
Age, Customized Age · 11 - 20 yr	10 Participants n=5 Participants	18 Participants n=7 Participants	9 Participants n=5 Participants	37 Participants n=4 Participants
Age, Customized Age · 21 - 40 yr	20 Participants n=5 Participants	19 Participants n=7 Participants	31 Participants n=5 Participants	70 Participants n=4 Participants
Age, Customized Age · 41 - 60 yr	26 Participants n=5 Participants	26 Participants n=7 Participants	34 Participants n=5 Participants	86 Participants n=4 Participants
Age, Customized Age · => 61 yr	23 Participants n=5 Participants	23 Participants n=7 Participants	24 Participants n=5 Participants	70 Participants n=4 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	56 Participants n=7 Participants	68 Participants n=5 Participants	171 Participants n=4 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	65 Participants n=7 Participants	77 Participants n=5 Participants	213 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black	49 Participants n=5 Participants	54 Participants n=7 Participants	62 Participants n=5 Participants	165 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · White	49 Participants n=5 Participants	49 Participants n=7 Participants	62 Participants n=5 Participants	160 Participants n=4 Participants
Race/Ethnicity, Customized Race/Ethnicity · Other, >1 race, or unknown	20 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants	59 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic Ethnicity	18 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	63 Participants n=4 Participants
Prior history of epilepsy	80 Participants n=5 Participants	83 Participants n=7 Participants	97 Participants n=5 Participants	260 Participants n=4 Participants
Final Diagnosis Seizure/Status Epilepticus	104 Participants n=5 Participants	102 Participants n=7 Participants	128 Participants n=5 Participants	334 Participants n=4 Participants
Final Diagnosis Non-epileptic spell	11 Participants n=5 Participants	13 Participants n=7 Participants	13 Participants n=5 Participants	37 Participants n=4 Participants
Final Diagnosis Unable to adjudicate	3 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants

PRIMARY outcome

Timeframe: Within 60 minutes after the start of study drug infusion

Population: The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Intention to treat

Outcome measures

Measure	Fosphenytoin (FOS) n=118 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=121 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=145 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Clinical Cessation of Status Epilepticus - Intention to Treat	53 Participants	56 Participants	68 Participants

PRIMARY outcome

Timeframe: Within 60 minutes after the start of study drug infusion

Population: The analysis population for this outcome is the Per-protocol population, which is all patients who completed the study without major protocol deviations.

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. Per-protocol analysis

Outcome measures

Measure	Fosphenytoin (FOS) n=79 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=91 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=109 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Clinical Cessation of Status Epilepticus - Per-protocol Analysis	37 Participants	43 Participants	51 Participants

PRIMARY outcome

Timeframe: Within 60 minutes after the start of study drug infusion

Population: The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Determined by the absence of clinically apparent seizures and improving consciousness at 1 hour without other anticonvulsant medications. The Adjudicated outcomes analysis is different from Outcome measure 1 because a central clinical phenomenology core of four neurologists adjudicated from the medical records the time to seizure cessation, the time in status epilepticus before trial-drug initiation, and the cause of the seizure. For each enrollment, two neurologists from this core group conducted independent initial reviews and then determined a consensus or consulted a third adjudicator, as needed. Adjudicators were unaware of the treatment assignments and made determinations by medical record review.

Outcome measures

Measure	Fosphenytoin (FOS) n=118 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=121 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=145 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Clinical Cessation of Status Epilepticus - Adjudicated Outcomes Analysis	57 Participants	60 Participants	67 Participants

SECONDARY outcome

Timeframe: Admission to intensive care unit after start of study drug infusion, where the ICU is the initial inpatient unit for the patient

Population: The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

ICU admission is recorded as occurring only if the ICU is the initial inpatient unit for the patient.

Outcome measures

Measure	Fosphenytoin (FOS) n=118 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=121 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=145 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Admission to Intensive Care Unit	70 Participants	71 Participants	87 Participants

SECONDARY outcome

Timeframe: number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study

Population: The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Length of stay is determined by the number of calendar days after the day of ED arrival until hospital discharge or subject end-of-study.

Outcome measures

Measure	Fosphenytoin (FOS) n=118 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=121 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=145 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Length of ICU Stay	1 days Interval 0.0 to 3.0	1 days Interval 0.0 to 3.0	1 days Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: start of drug infusion to seizure cessation

Population: The analysis population here is different than Participant Flow because it includes only the patients who had this data available. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

The time to termination of seizures is the interval from the start of study drug infusion to cessation of clinically apparent seizure in those who meet the primary outcome.

Outcome measures

Measure	Fosphenytoin (FOS) n=15 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=10 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=14 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Minutes From Start of Trial Drug Infusion to Termination of Seizures for Patients With Treatment Success	11.7 minutes Interval 7.5 to 20.9	7.0 minutes Interval 4.6 to 14.9	10.5 minutes Interval 5.7 to 15.5

SECONDARY outcome

Timeframe: within 20 minutes

Population: The population is different than Participant flow because it is only those with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper.

Number of participants with seizure cessation within 20 minutes of study drug initiation for patients with treatment success. This outcome measure was only reported in the Supplementary materials to the Primary Paper.

Outcome measures

Measure	Fosphenytoin (FOS) n=53 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=55 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=68 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Seizure Cessation Within 20 Minutes for Patients With Treatment Success	43 Participants	43 Participants	53 Participants

SECONDARY outcome

Timeframe: length of hospital stay

Population: The difference from Participant Flow is because the total of 384 is from the first 400 patients and excludes 16 re-enrollers in the study. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Length of hospital stay in days

Outcome measures

Measure	Fosphenytoin (FOS) n=118 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=121 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=145 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Length of Hospital Stay	3 days Interval 1.0 to 6.0	3 days Interval 2.0 to 6.0	3 days Interval 1.0 to 7.0

OTHER_PRE_SPECIFIED outcome

Timeframe: within 60 minutes of the start of study drug infusion

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Life-threatening hypotension within 60 minutes of the start of study drug infusion

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Life Threatening Hypotension	4 Participants	2 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: within 60 minutes of the start of study drug infusion

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Life-threatening cardiac arrhythmia within 60 minutes of the start of study drug infusion

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Life-threatening Cardiac Arrhythmia	0 Participants	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: within 60 minutes of start of study drug infusion

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Endotracheal intubation within 60 minutes of start of study drug infusion

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Endotracheal Intubation	33 Participants	21 Participants	30 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: within 6 hours of the start of study drug infusions

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Acute anaphylaxis is defined as a clinical presentation consistent with life threatening allergic reaction occurring within 6 hours of the start of study drug infusions and manifested as urticaria in combination with either (1) a systolic blood pressure of < 90 mmHg sustained for greater than 5 minutes, or (2) objective evidence of airway obstruction, and for which the patient was treated with antihistamines and/or steroids.

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Acute Anaphylaxis	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Respiratory depression is defined as impairment of ventilation or oxygenation necessitating definitive endotracheal intubation and mechanical ventilation. It is distinct from intubations performed only for airway protection in those with decreased levels of consciousness. It does not include those getting only supraglottic airways or transient bag-valve-mask support.

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Acute Respiratory Depression	16 Participants	10 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Safety outcome: Hepatic transaminase or ammonia elevations

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Hepatic Transaminase or Ammonia Elevations	0 Participants	1 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Purple glove syndrome is defined as the presence of all three of the findings of the objective edema: discoloration, and pain in the distal extremity in which study drug was administered, with or without known extravasation, and for which there is no other evident etiology.

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Purple Glove Syndrome	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 30 days

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Safety outcome: Death

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Death	3 Participants	2 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 60 minutes to 12 hours after start of study drug infusion

Population: The first 400 patients were analyzed for this outcome. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

acute seizure recurrence 60 minutes to 12 hours after start of study drug infusion

Outcome measures

Measure	Fosphenytoin (FOS) n=125 Participants Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 Participants Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 Participants Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Number of Participants With Safety Outcome: Acute Seizure Recurrence	14 Participants	14 Participants	16 Participants

Adverse Events

Fosphenytoin (FOS)

Serious events: 57 serious events

Other events: 28 other events

Deaths: 3 deaths

Valproic Acid

Serious events: 46 serious events

Other events: 22 other events

Deaths: 2 deaths

Levetiracetam

Serious events: 64 serious events

Other events: 25 other events

Deaths: 7 deaths

Serious adverse events

Measure	Fosphenytoin (FOS) n=125 participants at risk Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 participants at risk Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 participants at risk Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Injury, poisoning and procedural complications Accidental overdose	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Psychiatric disorders Agitation	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Cardiac disorders Atrial fibrillation	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Bacteraemia	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Cardiac disorders Cardiac arrest	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.3% 2/150 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Cerebral infarction	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Cerebrovascular accident	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Cerebrovascular spasm	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Clostridium difficile colitis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Psychiatric disorders Conversion disorder	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.3% 2/150 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Convulsion	20.0% 25/125 • Number of events 26 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	18.4% 23/125 • Number of events 23 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	20.0% 30/150 • Number of events 32 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Vascular disorders Deep vein thrombosis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Psychiatric disorders Delirium	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Depressed level of consciousness	9.6% 12/125 • Number of events 12 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	7.2% 9/125 • Number of events 9 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	10.0% 15/150 • Number of events 15 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Device malfunction	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Dysphagia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Encephalopathy	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.7% 4/150 • Number of events 4 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Endocarditis	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Haemorrhage intracranial	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Hepatobiliary disorders Hepatic failure	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Vascular disorders Hypotension	5.6% 7/125 • Number of events 7 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	4.8% 6/125 • Number of events 6 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.7% 4/150 • Number of events 4 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Hypothermia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Infusion site extravasation	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Intestinal ischaemia	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Cardiac disorders Intracardiac thrombus	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Investigations Liver function test abnormal	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Pneumonia	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.7% 4/150 • Number of events 4 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Respiratory depression	12.0% 15/125 • Number of events 16 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	6.4% 8/125 • Number of events 8 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	6.7% 10/150 • Number of events 10 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	3.2% 4/125 • Number of events 4 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Respiratory tract infection	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Retroperitoneal haemorrhage	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.0% 3/150 • Number of events 3 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Sepsis	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Infections and infestations Septic shock	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Stridor	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Cardiac disorders Supraventricular tachycardia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Renal and urinary disorders Urinary retention	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Other adverse events

Measure	Fosphenytoin (FOS) n=125 participants at risk Administer 20 mg/Kg fosphenytoin intravenously up to a maximum dose of 1500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 1500 fosphenytoin over 10 minutes. Fosphenytoin	Valproic Acid n=125 participants at risk Administer 40 mg/Kg valproic acid intravenously up to a maximum dose of 3000 mg (75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 3000 valproic acidover 10 minutes. Valproic acid	Levetiracetam n=150 participants at risk Administer 60 mg/Kg levetiracetam intravenously up to a maximum dose of 4500 mg ( 75 Kg) over 10 minutes. Those weighing more than 75 Kg receive a fixed dose of 4500 levetiracetam over 10 minutes. Levetiracetam
Investigations Heart rate decreased	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Abdominal pain	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Psychiatric disorders Agitation	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Apnoea	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Cardiac disorders Arrhythmia	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Balance disorder	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Psychiatric disorders Conversion disorder	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Convulsion	2.4% 3/125 • Number of events 3 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	6.4% 8/125 • Number of events 8 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.7% 4/150 • Number of events 4 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Vascular disorders Deep vein thrombosis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Injury, poisoning and procedural complications Fall	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Renal and urinary disorders Haematuria	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Headache	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Hemiparesis	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Immune system disorders Hypersensitivity	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Hyperthermia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.0% 3/150 • Number of events 3 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.4% 3/125 • Number of events 3 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Vascular disorders Hypotension	5.6% 7/125 • Number of events 7 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.7% 4/150 • Number of events 4 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Infusion site extravasation	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Mediastinal haemorrhage	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Nausea	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Pancreatitis	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Partial seizures	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Postictal paralysis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Skin and subcutaneous tissue disorders Pruritus	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Pyrexia	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	2.0% 3/150 • Number of events 3 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Respiratory depression	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Somnolence	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Nervous system disorders Status epilepticus	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
General disorders Systemic inflammatory response syndrome	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Cardiac disorders Tachycardia	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/150 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Investigations Troponin increased	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.3% 2/150 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Respiratory, thoracic and mediastinal disorders Upper airway obstruction	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.00% 0/125 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	0.67% 1/150 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.
Gastrointestinal disorders Vomiting	0.80% 1/125 • Number of events 1 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.6% 2/125 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.	1.3% 2/150 • Number of events 2 • Data on adverse events were collected through the first 24 hours after enrollment, for the duration of the trial. All-Cause mortality data was collected for the first 400 subjects, which is why the numbers in the All-cause mortality section differ from Participant flow. The first 400 patients were used because of the prespecified stopping rule and the trial stopped for futility.

Additional Information

Jordan Elm, PhD Biostatistician

Medical University of South Carolina

Phone: 843-876-1605

Email: elmj@musc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place