Trial Outcomes & Findings for Progesterone for the Treatment of Traumatic Brain Injury III (NCT NCT00822900)

Last Updated: 2016-01-20

Results Overview

A measure of functional recovery: A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. Favorable outcome was defined via stratified dichotomy based on the severity of the initial injury. For subjects with a severe injury, a GOS-E of 3 or higher were considered to be a favorable outcome; for subjects with moderate-to-severe injury, a GOS-E of 5 or higher was considered to be a favorable outcome; for subjects with a moderate injury, a GOS-E of 7 or higher was considered to be a favorable outcome.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

882 participants

Primary outcome timeframe

6 months post randomization

Results posted on

2016-01-20

Participant Flow

A total of 882 patients underwent randomization at 49 trauma centers in the United States between April 5, 2010, and October 30, 2013. 442 patients were randomized to Progesterone Arm and 440 were randomized to Placebo Arm.

Participant milestones

Participant milestones
Measure	Progesterone	Placebo
Overall Study STARTED	442	440
Overall Study COMPLETED	334	347
Overall Study NOT COMPLETED	108	93

Reasons for withdrawal

Reasons for withdrawal
Measure	Progesterone	Placebo
Overall Study Withdrawal by Subject	14	14
Overall Study Lost to Follow-up	9	9
Overall Study Death	83	69
Overall Study Became a ward of the state	2	1

Baseline Characteristics

Progesterone for the Treatment of Traumatic Brain Injury III

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Progesterone n=442 Participants	Placebo n=440 Participants	Total n=882 Participants Total of all reporting groups
Age, Continuous	39 years STANDARD_DEVIATION 18 • n=5 Participants	38 years STANDARD_DEVIATION 17 • n=7 Participants	39 years STANDARD_DEVIATION 18 • n=5 Participants
Sex: Female, Male Female	118 Participants n=5 Participants	114 Participants n=7 Participants	232 Participants n=5 Participants
Sex: Female, Male Male	324 Participants n=5 Participants	326 Participants n=7 Participants	650 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	61 Participants n=5 Participants	64 Participants n=7 Participants	125 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	347 Participants n=5 Participants	343 Participants n=7 Participants	690 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Asian	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	70 Participants n=5 Participants	64 Participants n=7 Participants	134 Participants n=5 Participants
Race (NIH/OMB) White	330 Participants n=5 Participants	331 Participants n=7 Participants	661 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment United States	442 participants n=5 Participants	440 participants n=7 Participants	882 participants n=5 Participants
Index GCS score at randomization Moderate	129 participants n=5 Participants	125 participants n=7 Participants	254 participants n=5 Participants
Index GCS score at randomization Moderate to severe	234 participants n=5 Participants	238 participants n=7 Participants	472 participants n=5 Participants
Index GCS score at randomization Severe	79 participants n=5 Participants	77 participants n=7 Participants	156 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post randomization

Population: The primary analysis was conducted according to intention to treat.

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) Favorable Outcome	213 participants	232 participants
Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) Unfavorable	201 participants	184 participants
Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) Missing Data	28 participants	24 participants

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Mortality Subjects with events	83 participants	69 participants
Mortality Subjects without events	359 participants	371 participants

SECONDARY outcome

Timeframe: 6 months

A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Disability Rating Scale	2.9 units on a scale Standard Deviation 4.6	3.3 units on a scale Standard Deviation 5.1

SECONDARY outcome

Timeframe: within 6 months

Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis Subjects with events	76 participants	25 participants
Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis Subjects without events	366 participants	415 participants

SECONDARY outcome

Timeframe: within 6 months

Pulmonary embolism - Events were defined based on either positive chest computed tomography (CT) scanning or ventilation/perfusion lung scan (V/Q).

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Pulmonary Embolism Subjects with events	10 participants	13 participants
Potentially Associated Adverse Events: Pulmonary Embolism Subjects without events	432 participants	427 participants

SECONDARY outcome

Timeframe: within 6 months

Acute ischemic stroke - Events were defined based on either positive computed tomography (CT) scanning, magnetic resonance imaging (MRI), or neurologist diagnosis of cerebrovascular accident (CVA)

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Acute Ischemic Stroke Subjects with events	6 participants	13 participants
Potentially Associated Adverse Events: Acute Ischemic Stroke Subjects without events	436 participants	427 participants

SECONDARY outcome

Timeframe: within 6 months

DVT - Events were defined based on a positive Doppler ultrasound exam

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT) Subjects with events	50 participants	40 participants
Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT) Subjects without events	392 participants	400 participants

SECONDARY outcome

Timeframe: within 6 months

Unexplained increased liver enzymes (e.g. not due to liver injury ) - Events were defined based on aspartate transaminase (AST) and alanine transaminase (ALT) levels \> 500 U/L and/or total bilirubin levels \> 2.0 mg/dL.

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level Subjects with events	18 participants	14 participants
Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level Subjects without events	424 participants	426 participants

SECONDARY outcome

Timeframe: within 6 months

Sepsis - Events must have met Centers for Disease Control and Prevention (CDC) definition of sepsis. The definition includes that a patient ≤1 year of age has at least 1 of the following clinical signs or symptoms with no other recognized cause: fever (\>38°C rectal), hypothermia (\<37°C rectal), apnea, or bradycardia, and blood culture not done or no organisms detected in blood and no apparent infection at another site and physician institutes treatment for sepsis.

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Sepsis Subjects with events	9 participants	9 participants
Potentially Associated Adverse Events: Sepsis Subjects without events	433 participants	431 participants

SECONDARY outcome

Timeframe: within 6 months

Events must have met Centers for Disease Control and Prevention (CDC) definition of pneumonia. There are three specific types of pneumonia: clinically defined pneumonia, pneumonia with specific laboratory findings, and pneumonia in immunocompromised patients. There are specific algorithms to identify each pneumonia, which include x-ray findings, fever with no other cause, leukopenia or leukocytosis, altered mental status with no other cause (adults \>70 years old), new onset of purulent sputum, change in character of sputum, increase respiratory secretions, increase suctioning requirements, new onset or worsening cough, dyspnea, tachypnea, rales, bronchial breath sounds, or worsening gas exchange, increased oxygen requirements, or increased ventilator demand). Also, labs can identify pneumonia such as positive growth in blood culture, positive Gram stain, and histopathologic exam evidence.

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Pneumonia Subjects with events	142 participants	140 participants
Potentially Associated Adverse Events: Pneumonia Subjects without events	300 participants	300 participants

SECONDARY outcome

Timeframe: within 6 months

CNS infection - Events must have met Centers for Disease Control and Prevention (CDC) definition of CNS infection. The definition includes intracranial infection, Meningitis, ventriculitis, and spinal abscess without meningitis.

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Central Nervous System (CNS) Infection Subjects with events	5 participants	3 participants
Potentially Associated Adverse Events: Central Nervous System (CNS) Infection Subjects without events	437 participants	437 participants

SECONDARY outcome

Timeframe: within 6 months

Myocardial infarction - Events were defined based on serial cardiac enzyme elevation consistent with MI and/or new ST elevation on electrocardiogram (ECG) consistent with MI. Potentially associated adverse events (those events which are included as outcome measures) were specifically defined per the protocol, and the classification of an event as a PAAE was determined by the site. The reported name of the associated event, however, was subject to clinical judgement and case details; these were then further coded by the Principal Investigator. Since these data points do not share the same definition, there is no reason to expect perfect concordance. (For example, the potentially associated adverse event of myocardial infarction may include MedDRA codes other than myocardial infarction.)

Outcome measures

Outcome measures
Measure	Progesterone n=442 Participants	Placebo n=440 Participants
Potentially Associated Adverse Events: Myocardial Infarction (MI) Subjects with events	5 participants	5 participants
Potentially Associated Adverse Events: Myocardial Infarction (MI) Subjects without events	437 participants	435 participants

Adverse Events

Progesterone

Serious events: 246 serious events

Other events: 332 other events

Deaths: 0 deaths

Placebo

Serious events: 251 serious events

Other events: 330 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

David W. Wright, Associate Professor, Department of Emergency Medicine, Emory University

Emergency Neurosciences, Emergency Medicine, Emory University

Phone: 404-778-1709

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Progesterone n=442 participants at risk	Placebo n=440 participants at risk
Blood and lymphatic system disorders Anemia	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Coagulopathy	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.45% 2/442 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Atrial fibrillation	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.68% 3/440 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Atrial flutter	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Bradycardia	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Cardiac arrest	2.5% 11/442 • Number of events 11 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	1.6% 7/440 • Number of events 7 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Cardiac failure congestive	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Myocardial infarction	0.45% 2/442 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Pericardial effusion	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Supraventricular tachycardia	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.91% 4/440 • Number of events 4 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Tachycardia	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Ear and labyrinth disorders Hypoacusis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Ear and labyrinth disorders Vestibular disorder	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Endocrine disorders Diabetes insipidus	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Blindness	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Ulcerative keratitis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Abdominal compartment syndrome	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Ascites	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Colitis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Diarrhoea	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Dysphagia	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Gastrointestinal hemorrhage	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.68% 3/440 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Gastrointestinal perforation	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Ileus	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Pancreatitis	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Pneumoperitoneum	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Small intestinal obstruction	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Volvulus	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Vomiting	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Adverse drug reaction	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Chest pain	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Device occlusion	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Infusion site erythema	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Pyrexia	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Systemic inflammatory response syndrome	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Hepatobiliary disorders Biloma	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Hepatobiliary disorders Cholecystitis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Hepatobiliary disorders Cholelithiasis	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.

Other adverse events
Measure	Progesterone n=442 participants at risk	Placebo n=440 participants at risk
Gastrointestinal disorders Gastrointestinal hemorrhage	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Anemia	1.8% 8/442 • Number of events 9 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	2.5% 11/440 • Number of events 12 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Coagulopathy	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Leukocytosis	2.7% 12/442 • Number of events 13 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	1.4% 6/440 • Number of events 6 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Thrombocytopenia	0.90% 4/442 • Number of events 5 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	1.6% 7/440 • Number of events 7 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.68% 3/440 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Atrial fibrillation	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.91% 4/440 • Number of events 4 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Bradycardia	1.1% 5/442 • Number of events 6 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	2.3% 10/440 • Number of events 11 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Extrasystoles	0.45% 2/442 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Myocardial infarction	0.45% 2/442 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Supraventricular tachycardia	0.90% 4/442 • Number of events 4 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Tachycardia	2.9% 13/442 • Number of events 13 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	1.8% 8/440 • Number of events 11 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Cardiac disorders Ventricular tachycardia	0.45% 2/442 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Ear and labyrinth disorders Hypoacusis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Endocrine disorders Adrenal insufficiency	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Endocrine disorders Diabetes insipidus	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.45% 2/440 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Conjunctival oedema	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Diplopia	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Eye pain	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Mydriasis	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Eye disorders Vision blurred	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Constipation	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	1.1% 5/440 • Number of events 5 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Diarrhoea	0.45% 2/442 • Number of events 2 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Nausea	0.68% 3/442 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Gastrointestinal disorders Vomiting	1.4% 6/442 • Number of events 7 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.68% 3/440 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Adverse drug reaction	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Catheter site hemorrhage	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Chest pain	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Chills	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Edema peripheral	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Infusion site edema	2.7% 12/442 • Number of events 14 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.91% 4/440 • Number of events 5 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Infusion site erythema	1.6% 7/442 • Number of events 7 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.68% 3/440 • Number of events 3 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Infusion site extravasation	3.4% 15/442 • Number of events 16 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	2.0% 9/440 • Number of events 10 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Infusion site pain	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Local swelling	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Pyrexia	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
General disorders Systemic inflammatory response syndrome	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Hepatobiliary disorders Hepatitis alcoholic	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Immune system disorders Hypersensitivity	0.23% 1/442 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.00% 0/440 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
Infections and infestations Abdominal abscess	0.00% 0/442 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.	0.23% 1/440 • Number of events 1 • Within 6 month after the enrollment. Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.