StrokePhase 1NCT00283088
Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
A Phase 1 study testing hypothermia and tissue plasminogen activator in people with Stroke, run by University of California, San Diego at 7 sites in United States.
Trial summary
The purpose of this trial is to evaluate if it is safe to use tissue plasminogen activator (tPA) within 6 hours of stroke onset when combined with hypothermia. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stroke
- What is being tested?
- hypothermia and tissue plasminogen activator
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 7 sitesUnited States
- Study dates
- Oct 2003to May 2009
- Phase
- Phase 1
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 80
- All eligibility criteria for t-PA administration for acute ischemic stroke as outlined by the NINDS tPA Guidelines are met with the exception of time from onset
- Stroke onset within 6 hours prior to planned start of tPA
- Any subtype of ischemic stroke with NIHSS < 7 at the time hypothermia begins
Who cannot join
- Etiology other than ischemic stroke
- Item 1a on NIHSS>1 at the time of enrollment
- Symptoms resolving or NIHSS < 7 at the time hypothermia begins
- Contraindications to hypothermia, such as patients with known hematologic dyscrasias which affect thrombosis, (cryoglobulinemia, Sickle cell disease, serum cold agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis obliterans.
- Known co-morbid conditions likely to complicate therapy, e.g., end-stage cardiomyopathy, uncompensated arrhythmia, myopathy, liver disease severe enough to elevate bilirubin, history of pelvic or abdominal mass likely to compress inferior vena cava, IVC filters, dementia severe enough to prevent valid consent, end-stage AIDS, known thyroid deficiency, known renal insufficiency likely to impair meperidine (Demerol®) clearance
- Intracerebral hematoma
Show all 14Show fewer
- Any intraventricular hemorrhage
- SBP > 185 or < 100; DBP > 110 or < 50 mmHg
- Pregnancy in women of child-bearing potential (must have pregnancy test, urine or blood, prior to therapy).
- Medical conditions likely to interfere with patient assessment
- Known allergy to meperidine (Demerol®)
- Currently taking MAO-I class of medication or used within previous 14 days
- Life expectancy < 3 months
- Not likely to be available for long-term follow-up.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Hartford Hospital
Hartford, Connecticut, 06102
Herman Memorial Hospital
Houston, Texas, 77030
Stanford Medical Center
Palo Alto, California, 94304
University of California San Diego, Thornton Hospital
San Diego, California, 92037
Scripps Mercy Hospital
San Diego, California, 92103
University of California San Diego, Hillcrest Medical Center
San Diego, California, 92103
Saint Louis University Medical Center
St Louis, Missouri, 63110
About this study
Official title: Phase 1 Study of Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
The purpose of this trial is to evaluate if it is safe to use tissue plasminogen activator (tPA) within 6 hours of stroke onset when combined with hypothermia.
Read the detailed description
A stroke is usually caused by a blockage in one of the arteries that carries blood to the brain. Research has shown that tissue plasminogen activator (tPA)-a naturally occurring protein that opens blocked arteries by dissolving blood clots-activates the body's ability to dissolve recently formed blood clots and reduces or prevents the brain damage caused by a stroke.
The Food and Drug Administration (FDA) has approved the use of tPA for people having a stroke when taken within 3 hours of stroke onset, but not for those who arrive at the hospital more than 3 hours after stroke onset.
Researchers believe that a lower body temperature (hypothermia) may be beneficial while a stroke is happening because hypothermia may prevent further brain injury, or may make the stroke less damaging. In particular, hypothermia may make it possible to use tPA later than 3 hours after a stroke begins. This study will determine if it is safe to use tPA within 6 hours of the start of a stroke when combined with hypothermia.
Patients will receive a standard stroke evaluation, which includes blood tests, a computed tomography (CT) scan, complete physical and neurological examinations, and an electrocardiogram (EKG) to determine eligibility for the study.
Participants will be randomly assigned to a study group based on when their stroke began. Those who arrive at the hospital less than 3 hours from stroke onset will receive tPA alone or tPA with cooling (hypothermia). Those who arrive at the hospital 3 to 6 hours after stroke onset will be assigned to 1 of 4 groups-receiving either tPA alone, tPA with cooling, cooling alone, or standard medical care. Length of participation (including observation after the patient leaves the hospital) is 90 days.
This study is part of the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS), which allows researchers to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients in less than 2 hours, and finding ways to treat additional patients later.
- Conditions
- Stroke
- Being tested
- hypothermia, tissue plasminogen activator
- Keywords
- stroke, hypothermia, cooling, tissue plasminogen activator, tPA, thrombolysis
- Medical subject headings
- Stroke, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypothermiaProcedure or surgery
Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System.
Subjects are stratified by time to six groups.
tissue plasminogen activatorDrug
tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care. Receives: Drug: tissue plasminogen activator |
| Group 2 | Active comparator | Groups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care. Receives: Procedure: hypothermia; Drug: tissue plasminogen activator |
| Group 3 | No intervention | Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). |
| Group 4 | Active comparator | Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). Receives: Drug: tissue plasminogen activator |
| Group 5 | Active comparator | Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). Receives: Procedure: hypothermia |
| Group 6 | Active comparator | Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). Receives: Procedure: hypothermia; Drug: tissue plasminogen activator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and volume of hemorrhage on CT
Measured: 48 hours post onset
Secondary outcomes (5)
Incidence of AE and SAE
Measured: 90 days post onset
Mortality in both groups testing whether hypothermia improves mortality after stroke
Measured: 90 Day
NIHSS at the end of hypothermia
Measured: Hour 23.5 +/- 30 minutes of hypothermia
Modified Rankin and NIHSS
Measured: 30 and 90days
CT lesion volume
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2006 (estimated)
- Study startOct 2003
- Primary completionOct 2008
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Investigators
- Patrick Lyden, MD, Principal investigator, University of California San Diego, Stroke Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00283088
- Sponsor's protocol ID
- P50NS44148LYDEN
- Other IDs
- P50NS044148
- Status last verified
- Jan 2009
- First submitted
- 26 Jan 2006
- Last updated
- 12 Jan 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lyden PD, Allgren RL, Ng K, Akins P, Meyer B, Al-Sanani F, Lutsep H, Dobak J, Matsubara BS, Zivin J. Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis. 2005 May-Jun;14(3):107-14. doi: 10.1016/j.jstrokecerebrovasdis.2005.01.001.
PubMed 17904009Guluma KZ, Hemmen TM, Olsen SE, Rapp KS, Lyden PD. A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology. Acad Emerg Med. 2006 Aug;13(8):820-7. doi: 10.1197/j.aem.2006.03.559. Epub 2006 Jun 9.
PubMed 16766740Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, Wijman CA, Rapp KS, Grotta JC, Lyden PD; ICTuS-L Investigators. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010 Oct;41(10):2265-70. doi: 10.1161/STROKEAHA.110.592295. Epub 2010 Aug 19.
PubMed 20724711Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007 Feb;38(2 Suppl):794-9. doi: 10.1161/01.STR.0000247920.15708.fa.
PubMed 17261741
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke
- ClinicalTrials.gov ID
- NCT00283088
- Acronym / sponsor ID
- P50NS44148LYDEN
- Conditions
- Stroke
- Keywords
- stroke, hypothermia, cooling, tissue plasminogen activator, tPA, thrombolysis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Oct 2003
- Primary completion
- Oct 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 27 Jan 2006 (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 purpose of this trial is to evaluate if it is safe to use tissue plasminogen activator (tPA) within 6 hours of stroke onset when combined with hypothermia.
Detailed description
A stroke is usually caused by a blockage in one of the arteries that carries blood to the brain. Research has shown that tissue plasminogen activator (tPA)-a naturally occurring protein that opens blocked arteries by dissolving blood clots-activates the body's ability to dissolve recently formed blood clots and reduces or prevents the brain damage caused by a stroke.
The Food and Drug Administration (FDA) has approved the use of tPA for people having a stroke when taken within 3 hours of stroke onset, but not for those who arrive at the hospital more than 3 hours after stroke onset.
Researchers believe that a lower body temperature (hypothermia) may be beneficial while a stroke is happening because hypothermia may prevent further brain injury, or may make the stroke less damaging. In particular, hypothermia may make it possible to use tPA later than 3 hours after a stroke begins. This study will determine if it is safe to use tPA within 6 hours of the start of a stroke when combined with hypothermia.
Patients will receive a standard stroke evaluation, which includes blood tests, a computed tomography (CT) scan, complete physical and neurological examinations, and an electrocardiogram (EKG) to determine eligibility for the study.
Participants will be randomly assigned to a study group based on when their stroke began. Those who arrive at the hospital less than 3 hours from stroke onset will receive tPA alone or tPA with cooling (hypothermia). Those who arrive at the hospital 3 to 6 hours after stroke onset will be assigned to 1 of 4 groups-receiving either tPA alone, tPA with cooling, cooling alone, or standard medical care. Length of participation (including observation after the patient leaves the hospital) is 90 days.
This study is part of the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS), which allows researchers to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients in less than 2 hours, and finding ways to treat additional patients later.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: tissue plasminogen activatorGroups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care. |
| Group 2 | Active comparator | Procedure: hypothermia, Drug: tissue plasminogen activatorGroups 1 and 2: Parallel groups, randomized to hypothermia or no hypothermia. Both groups receive tPA as a part of standard of care. |
| Group 3 | No intervention | –Groups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). |
| Group 4 | Active comparator | Drug: tissue plasminogen activatorGroups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). |
| Group 5 | Active comparator | Procedure: hypothermiaGroups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). |
| Group 6 | Active comparator | Procedure: hypothermia, Drug: tissue plasminogen activatorGroups 3, 4, 5 and 6: Factorial groups, randomized to hypothermia plus tPA, hypothermia alone, tPA alone, or no treatment assignment (standard of care). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 to 80
- All eligibility criteria for t-PA administration for acute ischemic stroke as outlined by the NINDS tPA Guidelines are met with the exception of time from onset
- Stroke onset within 6 hours prior to planned start of tPA
- Any subtype of ischemic stroke with NIHSS < 7 at the time hypothermia begins
Key exclusion criteria (14 listed)
- Etiology other than ischemic stroke
- Item 1a on NIHSS>1 at the time of enrollment
- Symptoms resolving or NIHSS < 7 at the time hypothermia begins
- Contraindications to hypothermia, such as patients with known hematologic dyscrasias which affect thrombosis, (cryoglobulinemia, Sickle cell disease, serum cold agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis obliterans.
- Known co-morbid conditions likely to complicate therapy, e.g., end-stage cardiomyopathy, uncompensated arrhythmia, myopathy, liver disease severe enough to elevate bilirubin, history of pelvic or abdominal mass likely to compress inferior vena cava, IVC filters, dementia severe enough to prevent valid consent, end-stage AIDS, known thyroid deficiency, known renal insufficiency likely to impair meperidine (Demerol®) clearance
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 |
|---|---|---|
| hypothermiaHypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System. Subjects are stratified by time to six groups. | Procedure or surgery | Group 2, Group 5, Group 6 |
| tissue plasminogen activatortPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots | Drug | Group 1, Group 2, Group 4, Group 6 |
Primary outcome
Incidence and volume of hemorrhage on CT
Time frame: 48 hours post onset
5 secondary outcomes
Incidence of AE and SAE
Time frame: 90 days post onset
Mortality in both groups testing whether hypothermia improves mortality after stroke
Time frame: 90 Day
NIHSS at the end of hypothermia
Time frame: Hour 23.5 +/- 30 minutes of hypothermia
Modified Rankin and NIHSS
Time frame: 30 and 90days
CT lesion volume
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2011.
- Background: PubMed 17904009Lyden PD, Allgren RL, Ng K, Akins P, Meyer B, Al-Sanani F, Lutsep H, Dobak J, Matsubara BS, Zivin J. Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis. 2005 May-Jun;14(3):107-14. doi: 10.1016/j.jstrokecerebrovasdis.2005.01.001.
- Background: PubMed 16766740Guluma KZ, Hemmen TM, Olsen SE, Rapp KS, Lyden PD. A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology. Acad Emerg Med. 2006 Aug;13(8):820-7. doi: 10.1197/j.aem.2006.03.559. Epub 2006 Jun 9.
- Background: PubMed 20724711Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, Wijman CA, Rapp KS, Grotta JC, Lyden PD; ICTuS-L Investigators. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010 Oct;41(10):2265-70. doi: 10.1161/STROKEAHA.110.592295. Epub 2010 Aug 19.
- Background: PubMed 17261741Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007 Feb;38(2 Suppl):794-9. doi: 10.1161/01.STR.0000247920.15708.fa.
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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.
Patrick Lyden, MD principal investigator
University of California San Diego, Stroke Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing hypothermia and tissue plasminogen activator in people with Stroke, run by University of California, San Diego at 7 sites in United States.
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 4 inclusion and 14 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: finished, as of the sponsor's last update on 12 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and volume of hemorrhage on CT (time frame: 48 hours post onset). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00283088, which also lists 4 linked publications.
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 12 Jan 2011.