Trial Outcomes & Findings for Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (NCT NCT00784134)

NCT ID: NCT00784134

Last Updated: 2018-12-05

Results Overview

Analysis modified on September 29, 2015 to account for adaptive randomization. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 500 participants
• Primary outcome timeframe: 180 days
• Results posted on: 2018-12-05

Participant Flow

Participant milestones

Measure	Alteplase Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Saline Placebo 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Overall Study STARTED	249	251
Overall Study COMPLETED	246	245
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Measure	Alteplase Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Saline Placebo 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Overall Study Lost to Follow-up	3	6

Baseline Characteristics

Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Baseline characteristics by cohort

Measure	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Total n=500 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	182 Participants n=5 Participants	172 Participants n=7 Participants	354 Participants n=5 Participants
Age, Categorical >=65 years	67 Participants n=5 Participants	79 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	117 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	134 Participants n=7 Participants	278 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	92 Participants n=5 Participants	78 Participants n=7 Participants	170 Participants n=5 Participants
Race (NIH/OMB) White	144 Participants n=5 Participants	161 Participants n=7 Participants	305 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Hungary	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment United States	190 participants n=5 Participants	180 participants n=7 Participants	370 participants n=5 Participants
Region of Enrollment Brazil	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Israel	13 participants n=5 Participants	24 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Switzerland	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Germany	21 participants n=5 Participants	18 participants n=7 Participants	39 participants n=5 Participants
Region of Enrollment Spain	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants

PRIMARY outcome

Timeframe: 180 days

Population: All the non-missing mRS scores at 180 days were analyzed.

Analysis modified on September 29, 2015 to account for adaptive randomization. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=245 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=246 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis	44.9 percentage of participants	47.6 percentage of participants

PRIMARY outcome

Timeframe: 180 days

Population: All the non-missing mRS scores at 180 days were analyzed.

The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=245 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=246 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis	4 mRS score Interval 3.0 to 6.0	4 mRS score Interval 3.0 to 5.0

PRIMARY outcome

Timeframe: 180 days

Population: All the non-missing mRS scores at 180 days were analyzed.

The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=245 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=246 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis	61.6 percentage of participants	64.2 percentage of participants

PRIMARY outcome

Timeframe: 180 days

Population: All the non-missing mRS scores at 180 days were analyzed.

The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=245 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=246 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3	44.9 percentage of participants	47.6 percentage of participants

PRIMARY outcome

Timeframe: 30 days and 180 days

Population: All the non-missing mRS scores at 30 days and 180 days were analyzed.

Comparing longitudinal modified Rankin Scale (mRS) scores 0-3 at Day 30 and Day 180. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=249 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=246 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3 Day 30	16.5 Percentage of participants	20.4 Percentage of participants
Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3 Day 180	45.7 Percentage of participants	48.0 Percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
All Cause Mortality	29.1 percentage of participants	18.5 percentage of participants

SECONDARY outcome

Timeframe: 72 hours

Population: All patients that were enrolled in CLEAR III were analyzed.

Change in blood volume measured between stability scan and end of treatment scan

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Clot Removal (Amount of Residual Blood)	0.97 odds ratio per time-weighted ml	0.96 odds ratio per time-weighted ml

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - Hospital Days	24 Number of days Interval 16.0 to 31.0	23 Number of days Interval 17.0 to 31.0

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - ICU Days	15 Number of days Interval 12.0 to 22.0	14 Number of days Interval 11.0 to 21.0

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - ICP Management	10.2 Percentage of events of ICP >20mmHg	9.8 Percentage of events of ICP >20mmHg

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - Mechanical Ventilation	76.5 % of participants with ventilation	73.9 % of participants with ventilation

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - Pressors	25.1 % of participants with pressors	24.1 % of participants with pressors

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - Shunts	17.5 % of participants with shunts	18.5 % of participants with shunts

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - All Infections	50.6 % of participants with infections	48.2 % of participants with infections

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - Pneumonia	32.7 % of participants with pneumonia	26.1 % of participants with pneumonia

SECONDARY outcome

Timeframe: 180 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Intensity of critical care management as measured by hospital and ICU length of stay, frequency of ICP >20 mmHg events, use of mechanical ventilation, pressors, and ventriculoperitioneal shunts, frequency of systemic infections.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Intensity of Critical Care Management - All Infections	56.2 % of participants with infections	49.8 % of participants with infections

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Safety/Mortality - Mortality Within 30 Days	14.3 Percentage of patients	8.8 Percentage of patients

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Safety/Mortality - Bacterial Brain Infections Within 30 Days	10.4 % of participants with brain infection	6.8 % of participants with brain infection

SECONDARY outcome

Timeframe: 72 hours

Population: All patients that were enrolled in CLEAR III were analyzed.

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Safety/Mortality - Systematic Bleeds Within 72 Hours	2.0 % of participants with systematic bleeds	2.4 % of participants with systematic bleeds

SECONDARY outcome

Timeframe: 30 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Frequency of bacterial brain infections, symptomatic brain bleeds, and mortality.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Safety/Mortality - Systematic Bleeds Within 30 Days	3.2 % of participants with systematic bleeds	3.6 % of participants with systematic bleeds

SECONDARY outcome

Timeframe: 180 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Assessment of number of adverse and serious adverse events by treatment group.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Adverse and Serious Adverse Events	60.2 percentage of participants	45.8 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients that were enrolled in CLEAR III were analyzed.

Cox Proportional Hazards Model is used to predict the hazards ratio by treatment group.

Outcome measures

Measure	Saline Placebo n=251 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=249 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Predicting Hazards of Death by Treatment Group	29.1 percentage of participants	18.5 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients that reported they were African-American with a non-missing mRS score at 180 days were analyzed.

Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=75 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=90 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American)	48.0 Percentage of participants	54.4 Percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients that reported they were White with a non-missing mRS score at 180 days were analyzed.

Assessment of modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=158 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=143 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White)	41.8 percentage of participants	43.4 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All female patients with a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=114 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=103 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female)	45.6 percentage of participants	47.6 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All male patients with a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=131 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=143 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male)	44.3 percentage of participants	47.6 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients 65 years of age or under with a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=167 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=179 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under)	52.1 Percentage of participants	53.6 Percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients over 65 years of age with a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=78 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=67 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years)	29.5 Percentage of participants	31.3 Percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients with an IVH size less than 20ml and a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=108 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=109 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml)	58.3 percentage of participants	55.1 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients with an IVH size between 20ml and 50ml and a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=109 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=110 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml)	38.5 percentage of participants	47.3 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients with an IVH size greater than 50ml and a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=28 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=27 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml)	17.9 percentage of participants	18.5 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients with a thalamic blood clot location and a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=139 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=147 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic)	37.4 percentage of participants	38.8 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All patients with a non-thalamic blood clot location and a non-missing mRS score at 180 days were analyzed.

Assessment of Modified Rankin Scale (mRS) score 0-3 compared by race, gender, age, IVH size, and ICH location. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 (perfect health without symptoms) to 6 (death).

Outcome measures

Measure	Saline Placebo n=106 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=99 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic)	54.7 percentage of participants	60.6 percentage of participants

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing Barthel scores at 180 days were analyzed.

Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The Barthel Index (BI) assesses ten functional tasks of daily living, and each task provides a measure for level of independence. Scores range from 0 and 100, with a higher score indicating greater independence.

Outcome measures

Measure	Saline Placebo n=170 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=197 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Functional Status - Barthel Index	69.5 Barthel score Standard Deviation 35.1	65.2 Barthel score Standard Deviation 37.7

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing eGOS scores at 180 days were analyzed.

Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The extended Glasgow Outcome Scale (eGOS) is a global scale for functional outcome with eight categories: 1 - Death, 2 - Vegetative State, 3 - Lower Severe Disability, 4 - Upper Severe Disability, 5 - Lower Moderate Disability, 6 - Upper Moderate Disability, 7 - Lower Good Recovery, 8 - Upper Good Recovery.

Outcome measures

Measure	Saline Placebo n=241 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=241 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability	77 % of participants with score>=4	95 % of participants with score>=4

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing NIHSS scores at 180 days were analyzed.

Assessment of NIHSS, Barthel Index, eGOS (dichotomy and ordinal) by group. The National Institutes of Health Stroke Scale (NIHSS) is a 15-item scale that assesses language, motor function, sensory loss, consciousness, visual fields, extraocular movements, coordination, neglect, and speech. It is scored from 0 (no stroke symptoms) to 42 (severe stroke).

Outcome measures

Measure	Saline Placebo n=158 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=182 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Functional Status - National Institutes of Health Stroke Scale (NIHSS)	2 NIHSS score Interval 0.0 to 7.0	3 NIHSS score Interval 0.0 to 9.0

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=165 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=186 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Strength	58.75 SIS score Standard Deviation 34.36	54.97 SIS score Standard Deviation 35.37

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=165 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=186 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Mobility	60.10 SIS score Standard Deviation 36.05	58.30 SIS score Standard Deviation 38.16

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=165 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=186 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Hand Function	56.52 SIS score Standard Deviation 39.69	53.41 SIS score Standard Deviation 41.86

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=165 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=186 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living	61.19 SIS score Standard Deviation 34.98	59.33 SIS score Standard Deviation 37.90

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=165 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=185 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Communication	79.60 SIS score Standard Deviation 26.76	76.02 SIS score Standard Deviation 31.47

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=165 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=185 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Thinking	62.68 SIS score Standard Deviation 31.18	58.48 SIS score Standard Deviation 33.11

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=163 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=185 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Emotion	73.45 SIS score Standard Deviation 20.24	73.14 SIS score Standard Deviation 19.62

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=163 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=186 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Participation	49.58 SIS score Standard Deviation 33.03	47.46 SIS score Standard Deviation 33.01

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing SIS scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. The Stroke Impact Scale (SIS) covers 8 dimensions of stroke outcomes: strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion, memory and thinking, participation. It is scored on a scale of 0 to 100 for each dimension, with higher scores indicating better self-reported health.

Outcome measures

Measure	Saline Placebo n=162 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=185 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - Stroke Impact Scale (SIS) - Recovery	63.44 SIS score Standard Deviation 25.44	60.04 SIS score Standard Deviation 26.42

SECONDARY outcome

Timeframe: 180 days

Population: All the non-missing EuroQol scores at 180 days were analyzed.

Assessment of SIS and EuroQol Visual Analog Scale by group. EuroQol Visual Analogue Scale (EQ-VAS) is a self-reported measure of health status. It is a marked scale where individuals draw a line to indicate their health, with end points of 0 (the worst health you can imagine) and 100 (the best health you can imagine).

Outcome measures

Measure	Saline Placebo n=160 Participants 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Alteplase n=177 Participants Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS)	65.1 EuroQol score Standard Deviation 23.3	62.8 EuroQol score Standard Deviation 26.0

Adverse Events

Alteplase

Serious events: 114 serious events

Other events: 165 other events

Deaths: 0 deaths

Saline Placebo

Serious events: 151 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alteplase n=249 participants at risk Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Saline Placebo n=251 participants at risk 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Infections and infestations Abdominal infection	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Cardiac disorders Acute coronary syndrome	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Renal and urinary disorders Acute renal failure	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	1.6% 4/251 • Number of events 4 • 180 days since symptom onset
Immune system disorders Allergic reaction	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Altered mental status	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Blood and lymphatic system disorders Anemia	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Nervous system disorders Anoxic brain damage	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Anoxic brain injury	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Aphasia	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Aspiration	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	2.4% 6/251 • Number of events 6 • 180 days since symptom onset
Cardiac disorders Asystole	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Cardiac disorders Atrial fibrillation	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Infections and infestations Bacteremia	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Brain and catheter related infection	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Brainstorming/autonomic dysfunction	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Infections and infestations Bronchial infection	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders COPD	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Cardiac disorders Cardiac arrest	2.0% 5/249 • Number of events 5 • 180 days since symptom onset	3.6% 9/251 • Number of events 9 • 180 days since symptom onset
Nervous system disorders Cerebrospinal fluid leakage	0.00% 0/249 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Nervous system disorders Cerebrovascular death (brain death)	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	2.4% 6/251 • Number of events 6 • 180 days since symptom onset
General disorders Cerebrovascular death (brain death)	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Renal and urinary disorders Chronic kidney disease	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Cognitive disturbance	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Gastrointestinal disorders Colitis	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Gastrointestinal disorders Colonic perforation	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Cardiac disorders Congestive heart failure	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Death due to index bleeding event	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
General disorders Death due to index bleeding event	4.0% 10/249 • Number of events 10 • 180 days since symptom onset	8.4% 21/251 • Number of events 21 • 180 days since symptom onset
Vascular disorders Deep vein thrombosis	2.4% 6/249 • Number of events 6 • 180 days since symptom onset	2.0% 5/251 • Number of events 5 • 180 days since symptom onset
Metabolism and nutrition disorders Dehydration	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Psychiatric disorders Delirium	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Depressed level of consciousness	2.8% 7/249 • Number of events 7 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Psychiatric disorders Depression	0.40% 1/249 • Number of events 3 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Metabolism and nutrition disorders Diabetes mellitus, Type I	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Diencephalic storming	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Gastrointestinal disorders Duodenal hemorrhage	0.80% 2/249 • Number of events 3 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Edema cerebral	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Nervous system disorders Encephalopathy	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Gastrointestinal disorders Enterocolitis	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Gastrointestinal disorders Esophageal hemorrhage	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Extensor posturing	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
General disorders Fever	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Injury, poisoning and procedural complications Fracture	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Gastrointestinal disorders Gastric hemorrhage	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Gastrointestinal disorders Gastroparesis	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Cardiac disorders Heart failure	0.00% 0/249 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Hepatobiliary disorders Hepatic failure	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Hepatobiliary disorders Hepatorenal syndrome	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Herniation	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Nervous system disorders Hydrocephalus	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Hydrocephalus, communicating	5.6% 14/249 • Number of events 14 • 180 days since symptom onset	5.2% 13/251 • Number of events 13 • 180 days since symptom onset
Nervous system disorders Hydrocephalus, obstructive	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Metabolism and nutrition disorders Hypernatremia	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Vascular disorders Hypertension	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Metabolism and nutrition disorders Hypoglycemia	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Metabolism and nutrition disorders Hyponatremia	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Vascular disorders Hypotension	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Hypoxia	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Investigations INR increased	0.00% 0/249 • 180 days since symptom onset	1.6% 4/251 • Number of events 4 • 180 days since symptom onset
Cardiac disorders Intercardiac clot	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Renal and urinary disorders Interstitial nephritis	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Intracranial abcess	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Catheter Tract, Enlargement	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Catheter Tract, New	3.2% 8/249 • Number of events 9 • 180 days since symptom onset	2.8% 7/251 • Number of events 7 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Hematoma, subdural	0.40% 1/249 • Number of events 2 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Subarachnoid Space, New	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Tissue, Enlargement	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Tissue, New	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	2.0% 5/251 • Number of events 5 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Ventricular system, Enlargement	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Ventricular system, New	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Nervous system disorders Intracranial hypertension	3.6% 9/249 • Number of events 9 • 180 days since symptom onset	3.2% 8/251 • Number of events 11 • 180 days since symptom onset
Hepatobiliary disorders Intrahepatic cholestasis of unk etiology	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Ischemia cerebrovascular	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Laryngeal edema	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Meningitis	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
General disorders Multi-organ failure	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Cardiac disorders Myocardial infarction	0.00% 0/249 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Cardiac disorders Myocarditis	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Surgical and medical procedures PEG Tube complication	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Infections and infestations Peritoneal infection	0.00% 0/249 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Psychiatric disorders Personality change	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Investigations Platelet count decreased	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Pneumonia	6.8% 17/249 • Number of events 19 • 180 days since symptom onset	5.2% 13/251 • Number of events 14 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.80% 2/251 • Number of events 2 • 180 days since symptom onset
Injury, poisoning and procedural complications Pulmonary embolism	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.8% 7/249 • Number of events 7 • 180 days since symptom onset	1.6% 4/251 • Number of events 4 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Renal and urinary disorders Renal calculi	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Renal and urinary disorders Renal insufficiency	2.4% 6/249 • Number of events 6 • 180 days since symptom onset	2.4% 6/251 • Number of events 6 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.8% 12/249 • Number of events 12 • 180 days since symptom onset	6.8% 17/251 • Number of events 17 • 180 days since symptom onset
Nervous system disorders Reversible cerebral vasoconstriction vs vasculitis	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Seizure	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Infections and infestations Sepsis	4.4% 11/249 • Number of events 13 • 180 days since symptom onset	2.8% 7/251 • Number of events 8 • 180 days since symptom onset
Cardiac disorders Sinus bradycardia	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Cardiac disorders Sinus tachycardia	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Stridor	1.6% 4/249 • Number of events 4 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Stroke	1.6% 4/249 • Number of events 4 • 180 days since symptom onset	1.6% 4/251 • Number of events 4 • 180 days since symptom onset
General disorders Sudden death NOS	2.4% 6/249 • Number of events 6 • 180 days since symptom onset	3.2% 8/251 • Number of events 8 • 180 days since symptom onset
Cardiac disorders Supraventricular tachydysrhythmia	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Gastrointestinal disorders Swollen tongue	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Tachypnea	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Cardiac disorders Takotsubo syndrome	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Blood and lymphatic system disorders Thrombocytopenia	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Tracheal mucositis	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Infections and infestations Tracheitis	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Injury, poisoning and procedural complications Tracheostomy site bleeding	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Infections and infestations Urinary tract infection	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	3.2% 8/251 • Number of events 9 • 180 days since symptom onset
Nervous system disorders VP shunt dysfunction	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Vasospasm or DIND	0.80% 2/249 • Number of events 2 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Cardiac disorders Ventricular fibrillation	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Infections and infestations Ventriculitis, bacterial	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Nervous system disorders Ventriculitis, bacterial	1.2% 3/249 • Number of events 3 • 180 days since symptom onset	4.0% 10/251 • Number of events 12 • 180 days since symptom onset
Infections and infestations Ventriculitis, non-bacterial	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset
Nervous system disorders Ventriculitis, non-bacterial	1.6% 4/249 • Number of events 4 • 180 days since symptom onset	1.2% 3/251 • Number of events 3 • 180 days since symptom onset
Gastrointestinal disorders Vomiting	0.00% 0/249 • 180 days since symptom onset	0.40% 1/251 • Number of events 1 • 180 days since symptom onset
Infections and infestations Wound infection, non-neurologic	0.40% 1/249 • Number of events 1 • 180 days since symptom onset	0.00% 0/251 • 180 days since symptom onset

Other adverse events

Measure	Alteplase n=249 participants at risk Administration of alteplase via the intraventricular catheter Alteplase: 1.0 mg of alteplase will be administered via the intraventricular catheter every 8 hours for up to 12 doses	Saline Placebo n=251 participants at risk 1 ml of normal saline administered via the intraventricular catheter Normal saline: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
Infections and infestations Bacteremia	5.2% 13/249 • Number of events 13 • 180 days since symptom onset	2.4% 6/251 • Number of events 7 • 180 days since symptom onset
Vascular disorders Deep vein thrombosis	8.4% 21/249 • Number of events 21 • 180 days since symptom onset	8.0% 20/251 • Number of events 20 • 180 days since symptom onset
Nervous system disorders Depressed level of consciousness	2.4% 6/249 • Number of events 7 • 180 days since symptom onset	4.8% 12/251 • Number of events 13 • 180 days since symptom onset
General disorders Fever	28.9% 72/249 • Number of events 76 • 180 days since symptom onset	26.7% 67/251 • Number of events 74 • 180 days since symptom onset
Nervous system disorders Hydrocephalus, communicating	9.6% 24/249 • Number of events 24 • 180 days since symptom onset	13.1% 33/251 • Number of events 33 • 180 days since symptom onset
Nervous system disorders Intracranial hemorrhage: Catheter Tract, New	13.7% 34/249 • Number of events 37 • 180 days since symptom onset	15.5% 39/251 • Number of events 47 • 180 days since symptom onset
Nervous system disorders Intracranial hypertension	15.7% 39/249 • Number of events 53 • 180 days since symptom onset	16.7% 42/251 • Number of events 50 • 180 days since symptom onset
Respiratory, thoracic and mediastinal disorders Pneumonia	16.5% 41/249 • Number of events 41 • 180 days since symptom onset	21.1% 53/251 • Number of events 53 • 180 days since symptom onset
Nervous system disorders Seizure	5.2% 13/249 • Number of events 14 • 180 days since symptom onset	6.4% 16/251 • Number of events 20 • 180 days since symptom onset
Infections and infestations Urinary tract infection	14.5% 36/249 • Number of events 38 • 180 days since symptom onset	9.2% 23/251 • Number of events 23 • 180 days since symptom onset

Additional Information

Dr. Daniel F. Hanley

Johns Hopkins University Division of Brain Injury Outcomes

Phone: 4106146996

Email: dhanley@jhmi.edu

Results disclosure agreements

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