Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke

NCT00283088 | Completed Phase 1 DMC

• 2 other identifiers: P50NS44148LYDENP50NS044148
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Stroke

Keywords

stroke; hypothermia; cooling; tissue plasminogen activator; tPA; thrombolysis

Outcome Measures

Primary Outcomes (1)

• Incidence and volume of hemorrhage on CT

  48 hours post onset

Secondary Outcomes (5)

• Incidence of AE and SAE

  90 days post onset

• Mortality in both groups testing whether hypothermia improves mortality after stroke

  90 Day

• NIHSS at the end of hypothermia

  Hour 23.5 +/- 30 minutes of hypothermia

• Modified Rankin and NIHSS

  30 and 90days

• CT lesion volume

  30 days

Study Arms (6)

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.

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.

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).

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).

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).

Procedure: hypothermia; Drug: tissue plasminogen activator

Interventions

hypothermia PROCEDURE

Hypothermia with or without tPA for stroke. Hypothermia is induced using the Celsius Control™ System. Subjects are stratified by time to six groups.

Group 2; Group 5; Group 6

tissue plasminogen activator DRUG

tPA is a naturally occurring protein that opens blocked arteries by dissolving blood clots

Group 1; Group 2; Group 4; Group 6

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (7)

Stanford Medical Center

Palo Alto, California, 94304, United States

Location

University of California San Diego, Thornton Hospital

San Diego, California, 92037, United States

Location

Scripps Mercy Hospital

San Diego, California, 92103, United States

Location

University of California San Diego, Hillcrest Medical Center

San Diego, California, 92103, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Saint Louis University Medical Center

St Louis, Missouri, 63110, United States

Location

Herman Memorial Hospital

Houston, Texas, 77030, United States

Location

Related Publications (4)

• 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.

  PMID: 17904009 BACKGROUND

• Guluma 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.

  PMID: 16766740 BACKGROUND

• Hemmen 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.

  PMID: 20724711 BACKGROUND

• Hemmen TM, Lyden PD. Induced hypothermia for acute stroke. Stroke. 2007 Feb;38(2 Suppl):794-9. doi: 10.1161/01.STR.0000247920.15708.fa.

  PMID: 17261741 BACKGROUND

MeSH Terms

Conditions

Stroke; Hypothermia

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Patrick Lyden, MD

  University of California San Diego, Stroke Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 26, 2006
• First Posted: January 27, 2006
• Study Start: October 1, 2003
• Primary Completion: October 1, 2008
• Study Completion: May 1, 2009
• Last Updated: January 12, 2011

Record last verified: 2009-01

Locations

US (7)