Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intraventricular Tissue Plasminogen Activator (tPA) in the Management of Aneurysmal Subarachnoid Hemorrhage

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01098890
Recruitment Status : Unknown
Verified April 2010 by University of Calgary.
Recruitment status was:  Recruiting
First Posted : April 5, 2010
Last Update Posted : November 11, 2010
Sponsor:
Information provided by:
University of Calgary

Tracking Information
First Submitted Date  ICMJE April 1, 2010
First Posted Date  ICMJE April 5, 2010
Last Update Posted Date November 11, 2010
Study Start Date  ICMJE October 2009
Estimated Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2010)
Determine rate and variance of ventricular and cisternal clot clearance (with and without TPA). [ Time Frame: 8 Days post bleed ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01098890 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2010)
  • Confirm the safety of intraventricular TPA. [ Time Frame: 6 months ]
    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 ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intraventricular Tissue Plasminogen Activator (tPA) in the Management of Aneurysmal Subarachnoid Hemorrhage
Official Title  ICMJE Intraventricular Tissue Plasminogen Activator in the Management of Aneurysmal Subarachnoid Hemorrhage: a Randomized Controlled Pilot Study
Brief Summary

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:

  1. Estimate the rate and variance of hematoma clearance following aneurysmal SAH, thereby facilitating sample size determination for a subsequent larger study;
  2. 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);
  3. Confirm the safety of intraventricular TPA.
Detailed Description

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:

  1. The occurrence of vasospasm, as determined using transcranial Doppler ultrasonography
  2. The occurrence of radiographic vasospasm, using CT angiography.
  3. The occurrence of "clinical" (symptomatic) vasospasm
  4. The rate of catheter-related central nervous system infections
  5. Levels of cytokines, endothelin and matrix metalloproteases in cerebrospinal fluid (CSF) and plasma
  6. Levels of fibrin-derived products (FDP), TPA and plasminogen-activator inhibitor in CSF
  7. Levels of S100β and neuron-specific enolase (NSE) in CSF and serum
  8. Intracranial pressure
  9. Volume of CSF drainage
  10. Extended Glasgow Outcome Scale, modified Rankin scale, EuroQOL at 6 months post-SAH
  11. Duration that ventriculostomy is required; need for permanent shunt
  12. Fever burden
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Aneurysmal Subarachnoid Hemorrhage
  • Intraventricular Hemorrhage
Intervention  ICMJE
  • Drug: Tissue Plasminogen Activator
    2mg tPA will be given every twelve hours for a maximum of 5 doses
    Other Name: Cathflo
  • Drug: Placebo
    Placebo will be administered every 12 hours for a maximum of 5 doses.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Tissue Plasminogen Activator
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 2, 2010)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2012
Estimated Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients (> 18 years old) with a proven ruptured cerebral aneurysm
  • Aneurysm has been / will be treated with coil embolization
  • EVD has been / will be placed as part of routine care
  • Modified Fisher score is 4 (cisternal blood > 1 mm thick with concomitant IVH)
  • CT scan after EVD placement shows "stability" with no increase in the amount of intracranial blood (Note: there is sometimes layering of blood, especially in the occipital horns of the lateral ventricles, that develops during the first 24-48 hours after a ruptured aneurysm due to circulation of blood in the CSF - this does not necessarily constitute an exclusion criterion).
  • Study drug can be administered within 72 hours of the time of SAH.

Exclusion Criteria:

  • Concern expressed by endovascular neurosurgeon / interventional radiologist that aneurysm has only been incompletely treated / isolated by coil embolization.
  • Patient requires craniotomy and clipping of the culprit aneurysm.
  • CT scan performed post-EVD insertion OR post-coiling shows increase in amount of intracranial blood.
  • Uncorrected coagulation disturbance (INR > 1.5, PTT > 45); correction is permitted (if coagulation disturbance develops during the study, subsequent doses of TPA should simply be withheld until coagulation can be corrected).
  • Uncorrected thrombocytopenia (platelets < 50,000); correction with platelet transfusions is permitted.
  • Involvement in another clinical trial
  • Uncontrolled active internal hemorrhage
  • Known allergy to study drug
  • Patient is pregnant
  • Any other condition the investigator believes would place the subject at risk if included in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01098890
Other Study ID Numbers  ICMJE 22461
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Andreas Kramer, University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andreas Kramer, MD University of Calgary
PRS Account University of Calgary
Verification Date April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP