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

NCT01123161 | Terminated Phase 2 Results DMC

• 3 other identifiers: ICTuS2/3P50NS044148P50NS044227
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 31

Brief 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.

Conditions

Stroke, Acute

Keywords

Hypothermia; Molecular Mechanisms of Pharmacological Action; Cerebral Infarction; Hematologic Agents; Stroke; Nervous System Diseases; Vascular Diseases; Tissue Plasminogen Activator; Central Nervous System Diseases; Fibrinolytic Agents; Cardiovascular Agents; Body Temperature Changes; Brain Diseases; Cerebrovascular Disorders; Pharmacologic Actions; Signs and Symptoms; Fibrin Modulating Agents; Therapeutic Uses; Brain Ischemia; Cardiovascular Diseases; Brain Infarction; Plasminogen; cooling; tPA; thrombolysis

Outcome Measures

Primary Outcomes (5)

• 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.

  Modified Rankin describes disability: 0 is free of any disability or symptoms, 6 is death, and higher grades between 0 and 6 reflect progressively greater disability

  90 days

• Incidence of Any Intracranial Hemorrhage (ICH) Within 48 Hours of Stroke Onset

  Incidence (number) of any intracranial hemorrhage (ICH) (whether or not symptomatic) within 48 hours of stroke onset will be presented by treatment group and overall.

  48 hours

• Incidence of Any Symptomatic Intracranial Hemorrhage (sICH) Within 48 Hours of Stroke Onset

  Incidence (number) of Symptomatic ICH (sICH) within 48 hours of stroke onset will be presented by treatment group and overall. Patients with neuroworsening (4 or more point increase in NIHSS , or a decline in the NIHSS consciousness item 1A score of more than 1 point, or a motor deterioration lasting more than 8 hours, all not due to iatrogenic cause) and hemorrhage seen on brain images in whom the investigator attributes the clinical change to the hemorrhage.

  48 hours

• Incidence of Pneumonia

  Number subjects diagnosed with pneumonia according to CDC criteria will be presented by treatment group and overall, regardless of seriousness

  7 days or discharge whichever comes first

• 90 Day Mortality

  Mortality prior to the 90-day evaluation.

  90 days

Secondary Outcomes (2)

• The Barthel Index Measure of Activities of Daily Living;

  90 days

• NIHSS Scores at 90 Days

  90 days

Study Arms (2)

Group1: IV t-PA and normothermia

ACTIVE COMPARATOR

IV tpa and normothermia

Drug: Group1: IV t-PA and normothermia

Group 2 : IV t-PA and hypothermia and anti-shivering treatment

ACTIVE COMPARATOR

IV tpa and hypothermia and anti-shivering treatment

Device: hypothermia and anti-shivering treatment

Interventions

hypothermia and anti-shivering treatment DEVICE

Hypothermia is induced using the Celsius Control™ System. Shivering is treated with buspirone, meperidine and surface warming

Also known as: cooling

Group 2 : IV t-PA and hypothermia and anti-shivering treatment

Group1: IV t-PA and normothermia DRUG

Group 1 will t-PA as standard of care and normothermia

Group1: IV t-PA and normothermia

Eligibility Criteria

• Age: 22 Years - 82 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 22 to 82 years old inclusive
• Patient receiving IV rt-PA using standard guidelines
• NIHSS score ≥ 7 and ≤ 20 (right hemisphere) or ≥ 7 and ≤ 24 (left hemisphere) at the time of randomization
• Pre-stroke mRS 0-1
• Able to begin endovascular phase of hypothermia within 2 hours of tPA completion
• Written Informed Consent, signed and dated by the patient (or patient's authorized representative)

You may not qualify if:

• Etiology other than ischemic stroke
• Item 1a on NIHSS \> 1 at the time of randomization
• Clinical symptoms consistent with brainstem or cerebellar stroke
• 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
• 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
• 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 x. History of HIT (heparin induced thrombocytopenia)
• Pregnancy (All women of child-bearing potential must have a negative pregnancy test, urine or blood, prior to therapy.)
• Medical conditions likely to interfere with patient assessment.
• Known allergy to meperidine or buspirone
• Currently taking or used within previous 14 days MAO-I class of medication.
• Life expectancy \< 6 months
• Not likely to be available for long-term follow-up
• Use, or planned use, of intra-arterial thrombolysis, mechanical clot removal, or other experimental or approved acute therapy for this stroke event
• Chest radiograph or clinical presentation suggestive of pneumonia or clinically significant pulmonary edema at baseline.
• Temperature upon admission greater than or equal to 38°C

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (31)

University of Alabama Hospital

Birmingham, Alabama, 35249, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92658, United States

Location

University of California San Diego Health System

San Diego, California, 92093, United States

Location

Scripps Mercy Medical Center

San Diego, California, 92103, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Swedish Medical Center

Englewood, Colorado, 80113, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Gulf Coast Medical Center

Fort Myers, Florida, 33912, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

University of Miami, Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Intercoastal Medical Group

Sarasota, Florida, 34232, United States

Location

St. Joseph's Hospital

Tampa, Florida, 33607, United States

Location

Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

Parkview Hospital

Fort Wayne, Indiana, 46805, United States

Location

Ruan Neurology Clinic and Research Center

Des Moines, Iowa, 50314, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

North Memorial Medical Center

Robbinsdale, Minnesota, 55422, United States

Location

Saint Louis University Medical Center

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Seton Medical Center Austin

Austin, Texas, 78705, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Medical University Innsbruck

Innsbruck, Austria

Location

CHUV

Lausanne, Switzerland

Location

Related Publications (7)

• 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

• 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

• Lyden P, Ernstrom K, Raman R. Determinants of Pneumonia Risk During Endovascular Hypothermia. Ther Hypothermia Temp Manag. 2013 Mar;3(1):24-27. doi: 10.1089/ther.2012.0021.

  PMID: 23667781 BACKGROUND

• 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.

  PMID: 22466971 BACKGROUND

• 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.

  PMID: 20817376 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

• Lyden P, Hemmen T, Grotta J, Rapp K, Ernstrom K, Rzesiewicz T, Parker S, Concha M, Hussain S, Agarwal S, Meyer B, Jurf J, Altafullah I, Raman R; Collaborators. Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2). Stroke. 2016 Dec;47(12):2888-2895. doi: 10.1161/STROKEAHA.116.014200. Epub 2016 Nov 10.

  PMID: 27834742 DERIVED

MeSH Terms

Conditions

Stroke; Hypothermia; Cerebral Infarction; Nervous System Diseases; Vascular Diseases; Central Nervous System Diseases; Body Temperature Changes; Brain Diseases; Cerebrovascular Disorders; Signs and Symptoms; Brain Ischemia; Cardiovascular Diseases; Brain Infarction

Interventions

Cool-Down Exercise

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Pathologic Processes; Necrosis

Intervention Hierarchy (Ancestors)

Post-Exercise Recovery Techniques; Physical Therapy Modalities; Therapeutics; Rehabilitation; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Dr. Patrick Lyden
• Organization: Cedars-Sinai Medical Center

lydenp@cshs.org

310-423-5166

Study Officials

• Patrick D. Lyden, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

• Thomas M. Hemmen, MD, PhD

  University of California, San Diego

  STUDY DIRECTOR

• James C. Grotta, MD

  The University of Texas Health Science Center, Houston

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized to normothermia or hypothermia

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: May 14, 2010
• Study Start: June 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: May 1, 2015
• Last Updated: April 5, 2017
• Results First Posted: April 5, 2017

Record last verified: 2017-02

Locations

US (29); AU (1); CH (1)