Phase 3
N=500
Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III
Intraventricular Hemorrhage
Bottom Line
View on ClinicalTrials.gov: NCT00784134 ↗Enrolled (actual)
500
Serious AEs
53.0%
Results posted
Jul 2017
Primary outcome: Primary: Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis — 47.6; 44.9 percentage of participants — p=0.554
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Alteplase (Drug); Normal saline (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Johns Hopkins University
- Primary completion
- Jul 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Participants With Modified Rankin Scale (mRS) <=3 - Dichotomized Analysis |
47.6; 44.9 | 0.554 |
| PRIMARY Participant Score on the Modified Rankin Scale (mRS) - Ordinal Analysis |
4; 4 | 0.484 |
| PRIMARY Participants With Modified Rankin Scale (mRS) <=4 - Dichotomized Analysis |
64.2; 61.6 | 0.552 |
| PRIMARY Random Effects Assessment of Site Effect on Modified Rankin Scale (mRS) <= 3 |
47.6; 44.9 | 0.428 |
| PRIMARY Longitudinal Assessment of Participants With Modified Rankin Scale (mRS) <=3 |
20.4; 16.5; 48.0; 45.7 | 0.384 |
| SECONDARY All Cause Mortality |
18.5; 29.1 | 0.0056 sig |
| SECONDARY Clot Removal (Amount of Residual Blood) |
0.96; 0.97 | <0.001 sig |
| SECONDARY Intensity of Critical Care Management - Hospital Days |
23; 24 | 0.771 |
| SECONDARY Intensity of Critical Care Management - ICU Days |
14; 15 | 0.098 |
| SECONDARY Intensity of Critical Care Management - ICP Management |
9.8; 10.2 | 0.450 |
| SECONDARY Intensity of Critical Care Management - Mechanical Ventilation |
73.9; 76.5 | 0.501 |
| SECONDARY Intensity of Critical Care Management - Pressors |
24.1; 25.1 | 0.795 |
| SECONDARY Intensity of Critical Care Management - Shunts |
18.5; 17.5 | 0.784 |
| SECONDARY Intensity of Critical Care Management - All Infections |
49.8; 56.2 | 0.152 |
| SECONDARY Intensity of Critical Care Management - Pneumonia |
26.1; 32.7 | 0.105 |
| SECONDARY Intensity of Critical Care Management - All Infections |
49.8; 56.2 | 0.152 |
| SECONDARY Safety/Mortality - Mortality Within 30 Days |
8.8; 14.3 | 0.055 |
| SECONDARY Safety/Mortality - Bacterial Brain Infections Within 30 Days |
6.8; 10.4 | 0.202 |
| SECONDARY Safety/Mortality - Systematic Bleeds Within 72 Hours |
2.4; 2.0 | 0.771 |
| SECONDARY Safety/Mortality - Systematic Bleeds Within 30 Days |
3.6; 3.2 | 0.811 |
| SECONDARY Adverse and Serious Adverse Events |
45.8; 60.2 | 0.0017 sig |
| SECONDARY Predicting Hazards of Death by Treatment Group |
18.5; 29.1 | 0.006 sig |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (African-American) |
54.4; 48.0 | 0.410 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Race (White) |
43.4; 41.8 | 0.781 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Female) |
47.6; 45.6 | 0.773 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Gender (Male) |
47.6; 44.3 | 0.587 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (65 Years or Under) |
53.6; 52.1 | 0.775 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Age (Over 65 Years) |
31.3; 29.5 | 0.808 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Less Than 20ml) |
55.1; 58.3 | 0.625 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (20-50ml) |
47.3; 38.5 | 0.191 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by IVH Size (Greater Than 50ml) |
18.5; 17.9 | 0.949 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Thalamic) |
38.8; 37.4 | 0.812 |
| SECONDARY Sub-Group Analyses - Difference in Modified Rankin Scale (mRS) 0-3 Proportion by Location (Non-Thalamic) |
60.6; 54.7 | 0.394 |
| SECONDARY Functional Status - Barthel Index |
65.2; 69.5 | 0.312 |
| SECONDARY Functional Status - Participants With Extended Glasgow Outcome (eGOS) Score >=Upper Severe Disability |
95; 77 | 0.087 |
| SECONDARY Functional Status - National Institutes of Health Stroke Scale (NIHSS) |
3; 2 | 0.14 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Strength |
54.97; 58.75 | 0.312 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Mobility |
58.30; 60.10 | 0.65 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Hand Function |
53.41; 56.52 | 0.478 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Activities of Daily Living |
59.33; 61.19 | 0.634 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Communication |
76.02; 79.60 | 0.255 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Thinking |
58.48; 62.68 | 0.224 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Emotion |
73.14; 73.45 | 0.882 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Participation |
47.46; 49.58 | 0.551 |
| SECONDARY Quality of Life - Stroke Impact Scale (SIS) - Recovery |
60.04; 63.44 | 0.224 |
| SECONDARY Quality of Life - EuroQol Visual Analogue Scale (EQ-VAS) |
62.8; 65.1 | 0.376 |
Summary
The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).
Eligibility Criteria
Inclusion Criteria
- Age 18-80
- Symptom onset less than 24 hrs prior to diagnostic CT scan
- Spontaneous ICH less than or equal to 30 cc or primary IVH
- IVH obstructing 3rd and/or 4th ventricles
- ICH clot stability at 6 hours or more post IVC placement
- IVH clot stability at 6 hours or more post IVC placement
- Catheter tract bleeding stability 6 hours or more post IVC placement
- EVD placed per standard medical care
- SBP less than 200 mmHg sustained for 6 hours prior to drug administration
- Able to randomize within 72 hours of diagnostic CT scan
- Historical Rankin of 0 or 1
Exclusion Criteria
- Suspected or untreated ruptured cerebral aneurysm, AVM, or tumor
- Presence of a choroid plexus vascular malformation or Moyamoya
- Clotting disorders
- Platelet count less than 100, 000, INR greater than 1.4
- Pregnancy
- Infratentorial hemorrhage
- SAH at clinical presentation
- ICH/IVH enlargement that cannot be stabilized in the treatment time window
- Ongoing internal bleeding
- Superficial or surface bleeding
- Prior enrollment in the study
- Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
- Planned or simultaneous participation (between screening and Day-30) in another interventional medical investigation or clinical trial.
- No subject or legal representative to give written informed consent
Data sourced from ClinicalTrials.gov (NCT00784134). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.