Aneurysmal Subarachnoid HemorrhagePhase 2NCT01098890
Intraventricular Tissue Plasminogen Activator (tPA) in the Management of Aneurysmal Subarachnoid Hemorrhage
A Phase 2 study testing Tissue Plasminogen Activator in people with Aneurysmal Subarachnoid Hemorrhage and Intraventricular Hemorrhage, run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage, Intraventricular Hemorrhage
- What is being tested?
- Tissue Plasminogen Activator
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2009to Apr 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Foothills Medical Center
Calgary, Alberta, T2N 2T9
Andreas Kramer, M.D, 403-944-4749, andreas.kramer@albertahealthservices.ca
Stephanie Todd, BSc. MBT, CCRP, 403-944-3414, stephanie.todd@albertahealthservices.ca
About this study
Official title: Intraventricular Tissue Plasminogen Activator in the Management of Aneurysmal Subarachnoid Hemorrhage: a Randomized Controlled Pilot Study
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.
Read the 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:
- 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
- Being tested
- Tissue Plasminogen Activator, Placebo
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tissue Plasminogen ActivatorDrug
Also called Cathflo
2mg tPA will be given every twelve hours for a maximum of 5 doses
PlaceboDrug
Placebo will be administered every 12 hours for a maximum of 5 doses.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Placebo |
| 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. Receives: Drug: Tissue Plasminogen Activator |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 8 Days post bleed
Secondary outcomes (2)
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.
Measured: 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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2010 (estimated)
- Study startOct 2009
- Primary completionOct 2011 (estimated)
- Study completionApr 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Investigators
- Andreas Kramer, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01098890
- Sponsor's protocol ID
- 22461
- Status last verified
- Apr 2010
- First submitted
- 1 Apr 2010
- Last updated
- 11 Nov 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraventricular Tissue Plasminogen Activator in the Management of Aneurysmal Subarachnoid Hemorrhage: a Randomized Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT01098890
- Acronym / sponsor ID
- 22461
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Oct 2011 (estimated)
- Study completion
- Apr 2012 (estimated)
- First posted
- 5 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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 | Drug: Tissue Plasminogen ActivatorIntraventricular TPA will be administered every 12 hours for a total five doses. Patients will be followed for a total of 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tissue Plasminogen ActivatorAlso: Cathflo2mg tPA will be given every twelve hours for a maximum of 5 doses | Drug | tPA (tissue plaminogen activator) |
| PlaceboPlacebo will be administered every 12 hours for a maximum of 5 doses. | Drug | Placebo |
Primary outcome
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).
2 secondary outcomes
Confirm the safety of intraventricular TPA.
Time frame: 6 months
Assess feasibility of a future multi-center trial
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Kramer, MD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tissue Plasminogen Activator in people with Aneurysmal Subarachnoid Hemorrhage and Intraventricular Hemorrhage, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine rate and variance of ventricular and cisternal clot clearance (with and without TPA). (time frame: 8 Days post bleed). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2010.