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The proposed study is to evaluate the acceleration the clearance of intraventricular blood (IVH) and subarachnoid hemorrhage (SAH) following ruptured intracranial aneurysms, thereby ameliorating complications, such as cerebral vasospasm, hydrocephalus and intracranial hypertension.
The primary objectives are:
Outcome Measures:
Safety will be assessed through adverse events, hemorrhagic complications and the development of ventriculostomy-related infections.
The volume and clearance of intracranial blood will be determined (in ml) using computerized software, as well as validated semi-quantitative ordinal scales (SAH Sum Score, Modified Graeb Score). The amount of IVH and SAH will be assessed at baseline (day 0), 72 hours after treatment onset, and on post-SAH day 8.
Additional secondary outcomes will include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo will be administered every 12 hours for a total five doses. Patients will be followed for a total of 6 months. |
|
| tPA (tissue plaminogen activator) | Active Comparator | Intraventricular TPA will be administered every 12 hours for a total five doses. Patients will be followed for a total of 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tissue Plasminogen Activator | Drug | 2mg tPA will be given every twelve hours for a maximum of 5 doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Determine rate and variance of ventricular and cisternal clot clearance (with and without TPA). | In order to plan the sample size for a future "proof-of-concept" trial, we need to better define the primary endpoint (the rate of ventricular and cisternal clot clearance, as well as the degree of variance in this rate, both with and without TPA). | 8 Days post bleed |
| Measure | Description | Time Frame |
|---|---|---|
| Confirm the safety of intraventricular TPA. | Intrathecal TPA has been administered to many hundreds of patients world-wide, and continues to be widely used despite a paucity of strong evidence demonstrating efficacy. Thus, we believe the safety has been relatively well established. On the other hand, much of the existing data is observational and retrospective, and could therefore be vulnerable to reporting bias. Experience is more limited among patients who have been managed with endovascular coil embolization, such that our study will provide important additional safety information. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andreas Kramer, MD | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Foothills Medical Center | Recruiting | Calgary | Alberta | T2N 2T9 | Canada |
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| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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| Placebo | Drug | Placebo will be administered every 12 hours for a maximum of 5 doses. |
|
| 6 months |
| Assess feasibility of a future multi-center trial | By performing a single center, prospective, randomized, double-blind, placebo-controlled trial, we will be able to (1) Estimate the recruitment rate; (2) Establish whether clinicians can be successfully blinded to treatment allocation (TPA vs. placebo); (3) Ensure that clinicians will comply with a treatment protocol | 6 months |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |