Trial Outcomes & Findings for Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (NCT NCT00894803)

NCT ID: NCT00894803

Last Updated: 2014-04-17

Results Overview

Primary safety outcome measure - Any ICH related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH. Judgment of significant neurological decline was made by the local clinical investigator

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 126 participants
• Primary outcome timeframe: Within 36 hours of initiation of therapy
• Results posted on: 2014-04-17

Participant Flow

The trial was conducted in emergency departments at 9 US medical centers comprised of 21 hospitals. Subjects were recruited between July 2009 and October 2012.

No enrolled participants were excluded from the trial before assignment to groups.

Participant milestones

Measure	Rt-PA and Eptifibatide recombinant tissue Plasminogen Activator (rt-PA; 0.6 mg/kg) and Epifibatide (225 mcg/kg)	Rt-PA Only recombinant tissue Plasminogen Activator (rt-PA; 0.9 mg/kg)
Overall Study STARTED	101	25
Overall Study COMPLETED	81	20
Overall Study NOT COMPLETED	20	5

Reasons for withdrawal

Measure	Rt-PA and Eptifibatide recombinant tissue Plasminogen Activator (rt-PA; 0.6 mg/kg) and Epifibatide (225 mcg/kg)	Rt-PA Only recombinant tissue Plasminogen Activator (rt-PA; 0.9 mg/kg)
Overall Study Death	20	4
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke

Baseline characteristics by cohort

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)	Total n=126 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	37 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants	64 Participants n=7 Participants	82 Participants n=5 Participants
Age, Continuous	75.5 Years n=5 Participants	71.6 Years n=7 Participants	74.2 Years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	48 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	53 Participants n=7 Participants	66 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	101 participants n=7 Participants	126 participants n=5 Participants
National Institutes of Health Stroke Scale Score (NIHSS) NIHSS <=12	10 Participants n=5 Participants	56 Participants n=7 Participants	66 Participants n=5 Participants
National Institutes of Health Stroke Scale Score (NIHSS) NIHSS >12	15 Participants n=5 Participants	45 Participants n=7 Participants	60 Participants n=5 Participants
National Institutes of Health Stroke Scale Score (NIHSS)	17 units on a scale n=5 Participants	12 units on a scale n=7 Participants	12 units on a scale n=5 Participants
Stroke symptom onset to intravenous rt-PA start < 1 hour	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Stroke symptom onset to intravenous rt-PA start 1 to 2 hours	11 Participants n=5 Participants	56 Participants n=7 Participants	67 Participants n=5 Participants
Stroke symptom onset to intravenous rt-PA start >2 to 3 hours	13 Participants n=5 Participants	42 Participants n=7 Participants	55 Participants n=5 Participants
Stroke symptom onset to intravenous rt-PA start > 3 hours	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Stroke symptom onset to intravenous rt-PA start	129 minutes n=5 Participants	113 minutes n=7 Participants	116 minutes n=5 Participants
Modified Rankin Score (mRS) 0	16 participants n=5 Participants	74 participants n=7 Participants	90 participants n=5 Participants
Modified Rankin Score (mRS) 1	2 participants n=5 Participants	11 participants n=7 Participants	13 participants n=5 Participants
Modified Rankin Score (mRS) 2	3 participants n=5 Participants	7 participants n=7 Participants	10 participants n=5 Participants
Modified Rankin Score (mRS) 3	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Modified Rankin Score (mRS) 4	0 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants
Modified Rankin Score (mRS) 5	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 36 hours of initiation of therapy

Primary safety outcome measure - Any ICH related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH. Judgment of significant neurological decline was made by the local clinical investigator

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset No sICH within 36 hours of treatment onset	22 participants	99 participants
Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours of Treatment Onset sICH within 36 hours of treatment onset	3 participants	2 participants

PRIMARY outcome

Timeframe: 90 days from treatment onset

Primary efficacy outcome measure - Modified Rankin Scale of 0 or 1 or return to the pre-stroke value at baseline or better. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days were given a value of '6', and assigned the "bad" outcome. Also those lost to follow-up were assigned the "bad" outcome.

The Modified Rankin Score (mRS) is a 6 point ordinal scale, measuring functional status. 0 (no symptoms at all), 5 (severe disability; bedridden, incontinent, and requiring constant nursing care).

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline mRS of 0-1 or return to baseline	9 participants	50 participants
Modified Rankin Scale (mRS) Score <1 or Return to mRS Baseline mRS >1 and > baseline	16 participants	51 participants

SECONDARY outcome

Timeframe: 90 days from treatment onset

Barthel index score of ≥ 95. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days and those lost to follow-up were assigned the "bad" outcome.

The Barthel index is a score comprised of 10 individual items. Each item may be scored 0, 5, 10 or 15; not all items use the full range of 4 possible values. The individual items are summed to produce a total score between 0 and 100; where 0 is inferior performance and 100 is optimal. A score of ≥ 95 is usually considered excellent.

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Barthel Index ≥ 95 Barthel Index ≥ 95	11 participants	55 participants
Barthel Index ≥ 95 Barthel Index < 95	14 participants	46 participants

SECONDARY outcome

Timeframe: 90 days from treatment onset

Glasgow outcome scale score of 1 versus greater than 1. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days and those lost to follow-up were assigned the "bad" outcome.

The Glasgow Outcome Scale is scored; 1=good recovery, 2=moderately disabled, 3=severely disabled, 4=vegetative survival, 5=dead.

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Glasgow Outcome Scale (GOS) of 1 GOS =1	10 participants	52 participants
Glasgow Outcome Scale (GOS) of 1 GOS > 1	15 participants	49 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 7 days of treatment onset

Incidence of serious systemic bleeding defined as requiring transfusion of 2 or more units of packed red blood cells.

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Serious Systemic Bleeding Serious systemic bleeding	0 participants	1 participants
Serious Systemic Bleeding No Serious systemic bleeding	25 participants	100 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 7 days of treatment onset

Any ICH related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH. Judgment of significant neurological decline was made by the local clinical investigator

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset sICH within 7 days of treatment onset	3 participants	2 participants
Symptomatic Intracranial Hemorrhage (sICH) Within 7 Days of Treatment Onset No sICH within 7 days of treatment onset	22 participants	99 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 7 days of treatment onset

Any ICH observed on CT by the study site neuroradiologist and the independent study neuroradiologist; the central reader. The ICH would not be related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH,where judgment of significant neurological decline was made by the local clinical investigator. A third independent reader will make the final determination if there is disagreement between the treating investigator and the central reader

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset No asICH within 7 days of treatment onset	22 participants	85 participants
Asymptomatic Intracranial Hemorrhage (asICH) Within 7 Days of Treatment Onset asICH within 7 days of treatment onset	3 participants	16 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 7 days of treatment onset

Death due to any cause within 7 days of treatment onset

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Death Within 7 Days of Treatment Onset Death within 7 days of treatment onset	3 participants	12 participants
Death Within 7 Days of Treatment Onset No death within 7 days of treatment onset	22 participants	89 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 7 days of treatment onset

Death due to stroke within 7 days of treatment onset. Classified by blinded clinical investigators

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Death Due to Stroke Within 7 Days of Treatment Onset Death due to stroke within 7 days of treatment ons	3 participants	12 participants
Death Due to Stroke Within 7 Days of Treatment Onset No Death due to stroke within 7 days of treatment	22 participants	89 participants

POST_HOC outcome

Timeframe: Within 90 days of treatment onset

Death due to any cause within 90 days of treatment onset

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Death Within 90 Days of Treatment Onset Death within 90 days of treatment onset	4 participants	20 participants
Death Within 90 Days of Treatment Onset No death within 90 days of treatment onset	21 participants	81 participants

POST_HOC outcome

Timeframe: Within 90 days of treatment onset

Death due to stroke within 90 days of treatment onset. Classified by blinded clinical investigators

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Death Due to Stroke Within 90 Days of Treatment Onset No Death due to stroke within 90 days of treatment	21 participants	86 participants
Death Due to Stroke Within 90 Days of Treatment Onset Death due to stroke within 90 days of treatment on	4 participants	15 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 2 hours of treatment onset

Study subjects with an NIH stroke scale score of ≤ 5 at 2 hours from treatment onset, those sedated and unable to be evaluated by the NIHSS were assigned the "bad" outcome (n=1).

The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death.

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
NIH Stroke Scale Score (NIHSS) ≤ 5 NIHSS ≤ 5	6 participants	35 participants
NIH Stroke Scale Score (NIHSS) ≤ 5 NIHSS > 5	19 participants	66 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 24 hours of treatment onset

Study subjects with an NIH stroke scale score of ≤ 2 at 24 hours from treatment onset, those dead (n=1) or sedated and unable to be evaluated by the NIHSS were assigned the "bad" outcome (n=5).

The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death.

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
NIH Stroke Scale Score (NIHSS) ≤ 2 NIHSS ≤ 2	5 participants	27 participants
NIH Stroke Scale Score (NIHSS) ≤ 2 NIHSS > 2	20 participants	74 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 90 days from treatment onset

Study subjects with an NIH stroke scale score ≤ 2 points at 90 days from treatment onset compared to baseline value, those dead or unable to be evaluated by the NIHSS were assigned the "bad" outcome.

The NIH stroke scale score is scale based on 15 items individually scored between 0-2, 0-3 or 0-4 depending upon the item. The individual items are summed to produce a score between 0 and 42, where 0 indicates no deficit and 42 indicates death.

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days NIHSS ≤ 2	11 participants	45 participants
NIH Stroke Scale Score (NIHSS) ≤2 at 90 Days NIHSS > 2	14 participants	56 participants

POST_HOC outcome

Timeframe: 90 days from treatment onset

Modified Rankin Scale of 0 or 1. The scale was performed by a study site investigator not directly involved with acute treatment of the patient. Study subjects dead at 90 days were given a value of '6', and assigned the "bad" outcome. Also those lost to follow-up were assigned the "bad" outcome.

The Modified Rankin Score (mRS) is a 6 point ordinal scale, measuring functional status. 0 (no symptoms at all), 5 (severe disability; bedridden, incontinent, and requiring constant nursing care).

Outcome measures

Measure	Rt-PA Only n=25 Participants rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 Participants rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Modified Rankin Scale (mRS) of 0-1 mRS of 0-1	6 participants	44 participants
Modified Rankin Scale (mRS) of 0-1 mRS > 1	19 participants	57 participants

Adverse Events

Rt-PA Only

Serious events: 7 serious events

Other events: 17 other events

Deaths: 0 deaths

Rt-PA and Eptifibatide

Serious events: 26 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rt-PA Only n=25 participants at risk rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 participants at risk rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
Blood and lymphatic system disorders Anaemias nonhaemolytic and marrow depression	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Arteriosclerosis, stenosis, vascular insufficiency and necrosis	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Surgical and medical procedures Cardiac therapeutic procedures	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Central nervous system vascular disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Communication disorders and disturbances	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Cardiac disorders Coronary artery disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Deliria (incl confusion)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Embolism and thrombosis	8.0% 2/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Hepatobiliary disorders Gallbladder disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Gastrointestinal disorders Gastrointestinal haemorrhages NEC	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Gastrointestinal disorders Gastrointestinal inflammatory conditions	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Gastrointestinal disorders Gastrointestinal signs and symptoms	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
General disorders General system disorders NEC	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Renal and urinary disorders Genitourinary tract disorders NEC	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Cardiac disorders Heart failures	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Increased intracranial pressure and hydrocephalus	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Infections and infestations Infections - pathogen unspecified	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Injury, poisoning and procedural complications Injuries NEC	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Musculoskeletal and connective tissue disorders Muscle disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Neurological disorders NEC	8.0% 2/25 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Neuromuscular disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Pulmonary vascular disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Renal and urinary disorders Renal disorders (excl nephropathies)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Respiratory disorders NEC	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Respiratory tract infections	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Seizures (incl subtypes)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Vascular haemorrhagic disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Surgical and medical procedures Vascular therapeutic procedures	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.

Other adverse events

Measure	Rt-PA Only n=25 participants at risk rt-PA (0.9 mg/kg)	Rt-PA and Eptifibatide n=101 participants at risk rt-PA (0.6 mg/kg) and Epifibatide (225 mcg/kg)
General disorders Administration site reactions	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 6 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Injury, poisoning and procedural complications Administration site reactions	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Immune system disorders Allergic conditions	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Blood and lymphatic system disorders Anaemias nonhaemolytic and marrow depression	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Skin and subcutaneous tissue disorders Angioedema and urticaria	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Anxiety disorders and symptoms	8.0% 2/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	4.0% 4/101 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Arteriosclerosis, stenosis, vascular insufficiency and necrosis	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Infections and infestations Bacterial infectious disorders	4.0% 1/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
General disorders Body temperature conditions	12.0% 3/25 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	6.9% 7/101 • Number of events 7 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Metabolism and nutrition disorders Bone, calcium, magnesium and phosphorus metabolism disorders	4.0% 1/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Bronchial disorders (excl neoplasms)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Cardiac disorders Cardiac arrhythmias	20.0% 5/25 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	7.9% 8/101 • Number of events 9 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Cardiac disorders Cardiac disorder signs and symptoms	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Central nervous system vascular disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Changes in physical activity	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Cognitive and attention disorders and disturbances	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Cardiac disorders Coronary artery disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Decreased and nonspecific blood pressure disorders and shock	8.0% 2/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	4.0% 4/101 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Gastrointestinal disorders Dental and gingival conditions	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Depressed mood disorders and disturbances	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
General disorders Device issues	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Metabolism and nutrition disorders Electrolyte and fluid balance conditions	12.0% 3/25 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	15.8% 16/101 • Number of events 16 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Embolism and thrombosis	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Investigations Enzyme investigations NEC	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Skin and subcutaneous tissue disorders Epidermal and dermal conditions	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Eye disorders Eye disorders NEC	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Infections and infestations Fungal infectious disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Gastrointestinal disorders Gastrointestinal motility and defaecation conditions	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	8.9% 9/101 • Number of events 9 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
General disorders Gastrointestinal signs and symptoms	28.0% 7/25 • Number of events 7 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	14.9% 15/101 • Number of events 22 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
General disorders General system disorders NEC	16.0% 4/25 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Renal and urinary disorders Genitourinary tract disorders NEC	16.0% 4/25 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	6.9% 7/101 • Number of events 7 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Endocrine disorders Glucose metabolism disorders (incl diabetes mellitus)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	4.0% 4/101 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Metabolism and nutrition disorders Glucose metabolism disorders (incl diabetes mellitus)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	4.0% 4/101 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Investigations Haematology investigations (incl blood groups)	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Headaches	16.0% 4/25 • Number of events 4 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	20.8% 21/101 • Number of events 21 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Cardiac disorders Heart failures	8.0% 2/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Increased intracranial pressure and hydrocephalus	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Infections and infestations Infections - pathogen unspecified	12.0% 3/25 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	9.9% 10/101 • Number of events 10 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Injury, poisoning and procedural complications Injuries NEC	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Musculoskeletal and connective tissue disorders Joint disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Lower respiratory tract disorders (excl obstruction and infection)	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Musculoskeletal and connective tissue disorders Muscle disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders NEC	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	11.9% 12/101 • Number of events 14 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Neurological disorders NEC	20.0% 5/25 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	10.9% 11/101 • Number of events 11 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Neuromuscular disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	3.0% 3/101 • Number of events 3 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Reproductive system and breast disorders Penile and scrotal disorders (excl infections and inflammations)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Investigations Physical examination and organ system status topics	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Pleural disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Injury, poisoning and procedural complications Procedural related injuries and complications NEC	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Renal and urinary disorders Renal disorders (excl nephropathies)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Respiratory disorders NEC	8.0% 2/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	6.9% 7/101 • Number of events 10 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Respiratory tract infections	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Seizures (incl subtypes)	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Psychiatric disorders Sleep disorders and disturbances	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Nervous system disorders Sleep disturbances (incl subtypes)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	2.0% 2/101 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Gastrointestinal disorders Tongue conditions	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract disorders (excl infections)	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Renal and urinary disorders Urinary tract signs and symptoms	8.0% 2/25 • Number of events 2 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	5.0% 5/101 • Number of events 5 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Renal and urinary disorders Urolithiases	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Vascular disorders Vascular haemorrhagic disorders	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	11.9% 12/101 • Number of events 16 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Investigations Water, electrolyte and mineral investigations	0.00% 0/25 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.99% 1/101 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.
Blood and lymphatic system disorders White blood cell disorders	4.0% 1/25 • Number of events 1 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.	0.00% 0/101 • Up to 90 days from initiation of therapy Adverse events were documented as recorded in the medical record until discharge. The occurrence of adverse events from the time of hospital discharge to the 90 day visit was collected at the time of the 90 day visit.

Additional Information

Dr Arthur Pancioli

University of Cincinnati

Phone: 513-558-8087

Email: arthur.pancioli@uc.edu

Results disclosure agreements

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