The Intravascular Cooling in the Treatment of Stroke 2/3 Trial

Stroke, Acute Clinical Trial

— ICTuS2/3  

Official title:

Phase 2/3 Study of Intravenous Thrombolysis and Hypothermia for Acute Treatment of Ischemic Stroke

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01123161
• Other study ID #: ICTuS2/3
• Secondary ID: P50NS044148
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: April 27, 2010
• Last updated: May 21, 2015
• Start date: June 2010
• Est. completion date: April 2015

Study information

• Verified date: May 2015
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to determine whether the combination of thrombolysis and hypothermia is superior to thrombolysis alone for the treatment of acute ischemic stroke.

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.

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.

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.

There are two study groups - tPA alone or tPA with cooling (hypothermia). Participants will be randomly assigned to one of the two study groups. 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 120
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 22 Years to 82 Years

Eligibility

Inclusion Criteria:

1. Age 22 to 82 years old inclusive

2. Patient receiving IV rt-PA using standard guidelines (Appendix II) Page 23

3. NIHSS score = 7 and = 20 (right hemisphere) or = 7 and = 24 (left hemisphere) at the time of randomization

4. Pre-stroke mRS 0-1

5. Able to begin endovascular phase of hypothermia within 2 hours of tPA completion

6. Written Informed Consent, signed and dated by the patient (or patient's authorized representative)

Exclusion Criteria:

1. Etiology other than ischemic stroke

2. Item 1a on NIHSS > 1 at the time of randomization

3. Clinical symptoms consistent with brainstem or cerebellar stroke

4. Classic lacunar syndrome with imaging confirmation of small deep ischemia, but randomization will not be delayed for neuroimaging other than initial scan to exclude hemorrhage

5. Known contraindications to hypothermia, such as known hematologic dyscrasias that affect thrombosis (cryoglobulinemia, Sickle cell disease, serum cold agglutinins), or vasospastic disorders such as Raynaud's or thromboangiitis obliterans

6. Known co-morbid conditions that are likely to complicate therapy in the opinion of the investigator, e.g., i. Heart failure (NYHA class III and IV)* ii. Uncompensated arrhythmia iii. Severe Liver disease iv. History of pelvic or abdominal mass likely to compress inferior vena cava v. IVC filters vi. HIV positive vii. Clinically active hypo or hyperthyroidism viii. Renal insufficiency likely to impair meperidine clearance ix. Chronic ethanol abuse

7. Pregnancy (All women of child-bearing potential must have a negative pregnancy test, urine or blood, prior to therapy.)

8. Medical conditions likely to interfere with patient assessment.

9. Known allergy to meperidine or buspirone

10. Currently taking or used within previous 14 days MAO-I class of medication.

11. Life expectancy < 6 months

12. Not likely to be available for long-term follow-up

13. Use, or planned use, of intra-arterial thrombolysis, mechanical clot removal, or other experimental or approved acute therapy for this stroke event

14. Chest radiograph or clinical presentation suggestive of pneumonia at baseline.

15. Temperature upon admission greater than or equal to 38°C

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke
• Stroke, Acute

Intervention

Device:
• hypothermia
Hypothermia is induced using the Celsius Control™ System

Other:
• Group1: IV t-PA and normothermia
Group 1 will t-PA as standard of care and normothermia

Locations

Country	Name	City	State
Switzerland	CHUV	Lausanne
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	University of Colorado Hospital	Aurora	Colorado
United States	Seton Medical Center Austin	Austin	Texas
United States	Mercy Medical Center	Des Moines	Iowa
United States	Michigan State University	East Lansing	Michigan
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	University of Florida	Gainesville	Florida
United States	University of Texas Health Science Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	North Memorial Medical Center	Robbinsdale	Minnesota
United States	Scripps Mercy Medical Center	San Diego	California
United States	University of California	San Diego	California
United States	Intercoastal Medical Group	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Switzerland, 

References & Publications (6)

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. Epub 2006 Jun 9. — View Citation

Guluma KZ, Liu L, Hemmen TM, Acharya AB, Rapp KS, Raman R, Lyden PD. Therapeutic hypothermia is associated with a decrease in urine output in acute stroke patients. Resuscitation. 2010 Dec;81(12):1642-7. doi: 10.1016/j.resuscitation.2010.08.003. — View Citation

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. — View Citation

Lyden P, Ernstrom K, Cruz-Flores S, Gomes J, Grotta J, Mullin A, Rapp K, Raman R, Wijman C, Hemmen T. Determinants of effective cooling during endovascular hypothermia. Neurocrit Care. 2012 Jun;16(3):413-20. doi: 10.1007/s12028-012-9688-y. — View Citation

Lyden P, Ernstrom K, Raman R. Determinants of Pneumonia Risk During Endovascular Hypothermia. Ther Hypothermia Temp Manag. 2013 Mar;3(1):24-27. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome is the proportion of patients achieving a favorable outcome defined as Modified Rankin Scale score of 0 or 1, assessed 90 days after treatment.		90 days	No
Secondary	The NIH Stroke Scale measure of neurologic deficit; the Barthel Index measure of activities of daily living; the Modified Rankin Scale measure of the degree of disability or dependence in daily activities		90 days	No
Secondary	90 day mortality		90 days	No