Intraventricular Tissue Plasminogen Activator (tPA) in the Management of Aneurysmal Subarachnoid Hemorrhage
Recruitment status was: Recruiting
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:
- Estimate the rate and variance of hematoma clearance following aneurysmal SAH, thereby facilitating sample size determination for a subsequent larger study;
- Assess the feasibility of a randomized controlled trial of intraventricular tissue plasminogen activator (TPA) among patients with SAH (enrollment rate, ability to blind investigators, protocol compliance);
- Confirm the safety of intraventricular TPA.
Aneurysmal Subarachnoid Hemorrhage
Drug: Tissue Plasminogen Activator
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Intraventricular Tissue Plasminogen Activator in the Management of Aneurysmal Subarachnoid Hemorrhage: a Randomized Controlled Pilot Study|
- Determine rate and variance of ventricular and cisternal clot clearance (with and without TPA). [ Time Frame: 8 Days post bleed ] [ Designated as safety issue: No ]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).
- Confirm the safety of intraventricular TPA. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]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.
- Assess feasibility of a future multi-center trial [ Time Frame: 6 months ] [ Designated as safety issue: No ]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
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||April 2012|
|Estimated Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Placebo will be administered every 12 hours for a total five doses. Patients will be followed for a total of 6 months.
Placebo will be administered every 12 hours for a maximum of 5 doses.
Active Comparator: tPA (tissue plaminogen activator)
Intraventricular TPA will be administered every 12 hours for a total five doses. Patients will be followed for a total of 6 months.
Drug: Tissue Plasminogen Activator
2mg tPA will be given every twelve hours for a maximum of 5 doses
Other Name: Cathflo
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:
- The occurrence of vasospasm, as determined using transcranial Doppler ultrasonography
- The occurrence of radiographic vasospasm, using CT angiography.
- The occurrence of "clinical" (symptomatic) vasospasm
- The rate of catheter-related central nervous system infections
- Levels of cytokines, endothelin and matrix metalloproteases in cerebrospinal fluid (CSF) and plasma
- Levels of fibrin-derived products (FDP), TPA and plasminogen-activator inhibitor in CSF
- Levels of S100β and neuron-specific enolase (NSE) in CSF and serum
- Intracranial pressure
- Volume of CSF drainage
- Extended Glasgow Outcome Scale, modified Rankin scale, EuroQOL at 6 months post-SAH
- Duration that ventriculostomy is required; need for permanent shunt
- Fever burden
Please refer to this study by its ClinicalTrials.gov identifier: NCT01098890
|Foothills Medical Center|
|Calgary, Alberta, Canada, T2N 2T9|
|Principal Investigator:||Andreas Kramer, MD||University of Calgary|