Trial record 5 of 772 for:    Open Studies | "Hemorrhage"

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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2010 by University of Calgary.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Calgary
ClinicalTrials.gov Identifier:
NCT01098890
First received: April 1, 2010
Last updated: November 10, 2010
Last verified: April 2010
  Purpose

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.

Condition Intervention Phase
Aneurysmal Subarachnoid Hemorrhage
Intraventricular Hemorrhage
Drug: Tissue Plasminogen Activator
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 12
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)
Arms Assigned Interventions
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.
Drug: Placebo
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

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01098890

Locations
Canada, Alberta
Foothills Medical Center Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Andreas Kramer, M.D    403-944-4749    andreas.kramer@albertahealthservices.ca   
Contact: Stephanie Todd, BSc. MBT, CCRP    403-944-3414    stephanie.todd@albertahealthservices.ca   
Principal Investigator: Andreas Kramer, MD         
Sub-Investigator: John Wong, MD         
Sub-Investigator: David Zygun, MD         
Sub-Investigator: Michael Hill, MD         
Sponsors and Collaborators
University of Calgary
Investigators
Principal Investigator: Andreas Kramer, MD University of Calgary
  More Information

No publications provided

Responsible Party: Dr. Andreas Kramer, University of Calgary
ClinicalTrials.gov Identifier: NCT01098890     History of Changes
Other Study ID Numbers: 22461
Study First Received: April 1, 2010
Last Updated: November 10, 2010
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Cerebral Hemorrhage
Intracranial Hemorrhages
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on July 20, 2014