Trial Outcomes & Findings for Clinical Trial on Treatment of Intraventricular Hemorrhage (NCT NCT00650858)
NCT ID: NCT00650858
Last Updated: 2017-12-11
Results Overview
The number of subjects who died at or before the 30-day follow-up visit were determined as a measure of safety. If more than 50% of the subjects died at or before the 30-day follow-up visit, the study would have been stopped for full DSMB review.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
30 days
Results posted on
2017-12-11
Participant Flow
Recruitment began for protocol stage 1 in August 2005 and ended for protocol stage 2 on February 6, 2008. Subjects were screened by clinical stroke service personnel in the Emergency Department or by direct transfer from an outside hospital.
Participant milestones
| Measure |
0.3 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
36
|
|
Overall Study
COMPLETED
|
8
|
8
|
36
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clinical Trial on Treatment of Intraventricular Hemorrhage
Baseline characteristics by cohort
| Measure |
0.3 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 Participants
Stage 2 (Dose Optimization)
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
39 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
13 Participants
n=483 Participants
|
|
Age, Continuous
|
47.6 years
STANDARD_DEVIATION 9.8 • n=93 Participants
|
57.3 years
STANDARD_DEVIATION 8.3 • n=4 Participants
|
57.0 years
STANDARD_DEVIATION 10.2 • n=27 Participants
|
55.6 years
STANDARD_DEVIATION 10.3 • n=483 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
18 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
34 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=93 Participants
|
8 participants
n=4 Participants
|
31 participants
n=27 Participants
|
47 participants
n=483 Participants
|
|
Region of Enrollment
Canada
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
3 participants
n=27 Participants
|
3 participants
n=483 Participants
|
|
Region of Enrollment
Germany
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
1 participants
n=483 Participants
|
|
Region of Enrollment
United Kingdom
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
1 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: 30 daysThe number of subjects who died at or before the 30-day follow-up visit were determined as a measure of safety. If more than 50% of the subjects died at or before the 30-day follow-up visit, the study would have been stopped for full DSMB review.
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
30-day Mortality
|
1 Number of participants
|
1 Number of participants
|
6 Number of participants
|
PRIMARY outcome
Timeframe: 30 daysThe incidence of bacterial ventriculitis/meningitis was recorded to determine the safety of intraventricular administration of rt-PA. If 30% or more subjects experienced this event, the study would have been stopped for full DSMB review.
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
Incidence of Bacterial Ventriculitis, Meningitis
|
0 Number of participants
|
1 Number of participants
|
1 Number of participants
|
PRIMARY outcome
Timeframe: 30-daysThe rate of symptomatic brain bleeding events were recorded to determine the safety of intraventricular administrations of rt-PA. If 35% or more subjects experienced a symptomatic bleeding event prior to the 30-day follow-up visit, the study would have been stopped for a full DSMB review.
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
Rate of Symptomatic Bleeding Events
|
0 participants
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 3 daysDaily IVH clot volume resolution, as a percentage of stability CT IVH volume, averaged over the first 3 days, determined by CT scans
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 Participants
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
Average Daily Percentage Clot Size Resolution Over the First 3 Days
|
22.19 Percent of stability CT volume resolved
Interval 8.0 to 66.0
|
24.20 Percent of stability CT volume resolved
Interval 0.0 to 72.0
|
19.99 Percent of stability CT volume resolved
Interval 0.0 to 60.0
|
SECONDARY outcome
Timeframe: 90 days90 day follow-up visit mRS score. 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 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
90 Day Follow-Up Modified Rankin Scale (mRS) Score
|
—
|
—
|
4.3 mRS score
Interval 0.0 to 6.0
|
SECONDARY outcome
Timeframe: 90 days90 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=35 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
90 Day Follow-Up Glasgow Outcome Scale (GOS) Score
|
—
|
—
|
2.3 GOS score
Interval 0.0 to 4.0
|
SECONDARY outcome
Timeframe: 180 days180 day follow-up visit mRS score. 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 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=35 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
180 Day Follow-Up Modified Rankin Scale (mRS) Score
|
—
|
—
|
4.0 mRS score
Interval 0.0 to 6.0
|
SECONDARY outcome
Timeframe: 180 days180 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery. (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)
Outcome measures
| Measure |
0.3 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=35 Participants
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
180 Day Follow-Up Glasgow Outcome Scale (GOS) Score
|
—
|
—
|
2.3 GOS score
Interval 0.0 to 4.0
|
Adverse Events
0.3 mg Rt-PA q12h
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
1.0 mg Rt-PA q12h
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
1.0 mg Rt-PA q8h
Serious events: 11 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
0.3 mg Rt-PA q12h
n=8 participants at risk
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 participants at risk
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 participants at risk
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Accidental Extubation
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/36
|
|
Cardiac disorders
Cardiac Arrest
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
8.3%
3/36 • Number of events 3
|
|
Nervous system disorders
Cerebral Infarction
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Hemorrhage new catheter tract >5 mm with mass effect, symptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus, Communicating
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
ICH Hemorrhage, new symptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
IVH Hemorrhage enlargement - asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
IVH Hemorrhage enlargement - symptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
IVH hemorrhage, new symptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Seizure
|
0.00%
0/8
|
12.5%
1/8 • Number of events 2
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Suspected cardiac or pulmonary embolism
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal stricture
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Ventilatory failure, mechanical
|
12.5%
1/8 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Nervous system disorders
Ventriculitis, Bacterial
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 2
|
|
Nervous system disorders
Ventriculitis, non-bacterial
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
Other adverse events
| Measure |
0.3 mg Rt-PA q12h
n=8 participants at risk
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q12h
n=8 participants at risk
Stage 1 (Dose Finding)
|
1.0 mg Rt-PA q8h
n=36 participants at risk
Stage 2 (Dose Optimization)
|
|---|---|---|---|
|
Renal and urinary disorders
Acute Renal Failure
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
2.8%
1/36 • Number of events 1
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
3/36 • Number of events 3
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
5.6%
2/36 • Number of events 2
|
|
Blood and lymphatic system disorders
Bacteremia
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
3/36 • Number of events 4
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Nervous system disorders
Brain Edema / Swelling
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
3/36 • Number of events 3
|
|
Nervous system disorders
CSF Leak
|
0.00%
0/8
|
25.0%
2/8 • Number of events 2
|
0.00%
0/36
|
|
Nervous system disorders
Cerebral Infarction
|
0.00%
0/8
|
0.00%
0/8
|
13.9%
5/36 • Number of events 5
|
|
Nervous system disorders
Cerebral infarction, extension
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/36
|
|
Cardiac disorders
Congestive Heart Failure
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Nervous system disorders
Decreased Level of counciousness
|
37.5%
3/8 • Number of events 3
|
25.0%
2/8 • Number of events 2
|
19.4%
7/36 • Number of events 12
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Renal and urinary disorders
Diarrhea
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
3/36 • Number of events 3
|
|
Metabolism and nutrition disorders
Edema (metabolic causes)
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
2.8%
1/36 • Number of events 1
|
|
General disorders
Fever of unknown origin
|
37.5%
3/8 • Number of events 3
|
50.0%
4/8 • Number of events 4
|
22.2%
8/36 • Number of events 8
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
8.3%
3/36 • Number of events 4
|
|
Nervous system disorders
Hemorrhage enl, cath tract >5mm w/o mass, asym
|
0.00%
0/8
|
25.0%
2/8 • Number of events 2
|
5.6%
2/36 • Number of events 2
|
|
Nervous system disorders
Hemorrhage enlargement, catheter tract > 5 mm with mass effect, asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
5.6%
2/36 • Number of events 2
|
|
Nervous system disorders
Hemorrhage, new catheter tract <= 5 mm, asymptomatic
|
0.00%
0/8
|
37.5%
3/8 • Number of events 3
|
5.6%
2/36 • Number of events 2
|
|
Nervous system disorders
Hemorrhage, new catheter tract > 5 mm with mass effect, asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
5.6%
2/36 • Number of events 2
|
|
Nervous system disorders
Hemorrhage, new catheter tract > 5 mm with mass effect, symptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Herniation, Brain
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus, Obstructive
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/36
|
|
Nervous system disorders
Hydrocephalus, communicating
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
3/36 • Number of events 3
|
|
Blood and lymphatic system disorders
Hyperglycemia
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/36
|
|
Cardiac disorders
Hypertension
|
12.5%
1/8 • Number of events 1
|
37.5%
3/8 • Number of events 4
|
2.8%
1/36 • Number of events 1
|
|
Blood and lymphatic system disorders
Hypokalemia
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
8.3%
3/36 • Number of events 3
|
|
Blood and lymphatic system disorders
Hyponatremia
|
25.0%
2/8 • Number of events 2
|
0.00%
0/8
|
0.00%
0/36
|
|
Blood and lymphatic system disorders
Hypoxemia
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
ICH hemorrhage enlargement, asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
ICH hemorrhage, new asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
ICH hemorrhage, new symptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
IVH hemorrhage enlargement - asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
3/36 • Number of events 4
|
|
Blood and lymphatic system disorders
Increased Blood Urea Nitrogen
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Increased midline shift
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Intracranial hypertension
|
12.5%
1/8 • Number of events 5
|
25.0%
2/8 • Number of events 2
|
5.6%
2/36 • Number of events 4
|
|
Nervous system disorders
Peri-hemorrhagic ischemic change
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/8
|
0.00%
0/8
|
5.6%
2/36 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
12.5%
1/8 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
25.0%
9/36 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia, aspiration
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
8.3%
3/36 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
SAH Hemorrhage, new asymptomatic
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Nervous system disorders
Siezure
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
2.8%
1/36 • Number of events 1
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/8
|
0.00%
0/8
|
5.6%
2/36 • Number of events 2
|
|
Infections and infestations
Skin Exanthema
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Tracheitis
|
0.00%
0/8
|
0.00%
0/8
|
2.8%
1/36 • Number of events 1
|
|
Renal and urinary disorders
Urinary tract infection
|
12.5%
1/8 • Number of events 1
|
25.0%
2/8 • Number of events 2
|
11.1%
4/36 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Ventilatory failure
|
0.00%
0/8
|
0.00%
0/8
|
5.6%
2/36 • Number of events 2
|
|
Nervous system disorders
Ventriculitis, bacterial
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
5.6%
2/36 • Number of events 4
|
|
Nervous system disorders
Ventriculitis, non-bacterial
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
22.2%
8/36 • Number of events 9
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI shall provide the sponsor with a copy of any proposed publication for review and comment thirty (30) days prior to submission. JHU may request a delay in publication, not to exceed 90 days if it is necessary to protect any intellectual property.
- Publication restrictions are in place
Restriction type: OTHER