TY - JOUR

T1 - EuroHYP-1

T2 - European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke

AU - van der Worp, H Bart

AU - Macleod, Malcolm R

AU - Bath, Philip M W

AU - Demotes, Jacques

AU - Durand-Zaleski, Isabelle

AU - Gebhardt, Bernd

AU - Gluud, Christian

AU - Kollmar, Rainer

AU - Krieger, Derk W

AU - Lees, Kennedy R

AU - Molina, Carlos

AU - Montaner, Joan

AU - Roine, Risto O

AU - Petersson, Jesper

AU - Staykov, Dimitre

AU - Szabo, Istvan

AU - Wardlaw, Joanna M

AU - Schwab, Stefan

AU - EuroHYP-1 investigators

N1 - © 2014 World Stroke Organization.

PY - 2014/7

Y1 - 2014/7

N2 - RATIONALE: Cooling reduced infarct size and improved neurological outcomes in animal studies modeling ischemic stroke, and also improved outcome in randomized clinical trials in patients with hypoxic-ischemic brain injury after cardiac arrest. Cooling awake patients with ischemic stroke has been shown feasible in phase II clinical trials.PRIMARY AIM: To determine whether systemic cooling to a target body temperature between 34·0 and 35·0°C, started within six-hours of symptom onset and maintained for 24 h, improves functional outcome at three-months in patients with acute ischemic stroke.DESIGN: International, multicenter, phase III, randomized, open-label clinical trial with blinded outcome assessment in 1500 patients aged 18 years or older with acute ischemic stroke and a National Institutes of Health Stroke Scale score of 6 up to and including 18. In patients randomized to hypothermia, cooling to a target body temperature of 34-35°C will be started within six-hours after symptom onset with rapid intravenous infusion of refrigerated normal saline or a surface cooling technique and maintained for 24 h with a surface or endovascular technique. Patients randomized to hypothermia will receive pethidine and buspirone to prevent shivering and discomfort.PRIMARY OUTCOME: Score on the modified Rankin Scale at 91 days, as analyzed with ordinal logistic regression and expressed as a common odds ratio.DISCUSSION: With 750 patients per intervention group, this trial has 90% power to detect 7% absolute improvement at the 5% significance level. The full trial protocol is available at http://www.eurohyp1.eu. ClinicalTrials.gov Identifier: NCT01833312.

AB - RATIONALE: Cooling reduced infarct size and improved neurological outcomes in animal studies modeling ischemic stroke, and also improved outcome in randomized clinical trials in patients with hypoxic-ischemic brain injury after cardiac arrest. Cooling awake patients with ischemic stroke has been shown feasible in phase II clinical trials.PRIMARY AIM: To determine whether systemic cooling to a target body temperature between 34·0 and 35·0°C, started within six-hours of symptom onset and maintained for 24 h, improves functional outcome at three-months in patients with acute ischemic stroke.DESIGN: International, multicenter, phase III, randomized, open-label clinical trial with blinded outcome assessment in 1500 patients aged 18 years or older with acute ischemic stroke and a National Institutes of Health Stroke Scale score of 6 up to and including 18. In patients randomized to hypothermia, cooling to a target body temperature of 34-35°C will be started within six-hours after symptom onset with rapid intravenous infusion of refrigerated normal saline or a surface cooling technique and maintained for 24 h with a surface or endovascular technique. Patients randomized to hypothermia will receive pethidine and buspirone to prevent shivering and discomfort.PRIMARY OUTCOME: Score on the modified Rankin Scale at 91 days, as analyzed with ordinal logistic regression and expressed as a common odds ratio.DISCUSSION: With 750 patients per intervention group, this trial has 90% power to detect 7% absolute improvement at the 5% significance level. The full trial protocol is available at http://www.eurohyp1.eu. ClinicalTrials.gov Identifier: NCT01833312.

KW - Analgesics, Opioid

KW - Anti-Anxiety Agents

KW - Brain Ischemia

KW - Buspirone

KW - Clinical Protocols

KW - Europe

KW - Humans

KW - Hypothermia, Induced

KW - Logistic Models

KW - Meperidine

KW - Molecular Sequence Data

KW - Outcome Assessment (Health Care)

KW - Patient Selection

KW - Severity of Illness Index

KW - Stroke

KW - Treatment Outcome

U2 - 10.1111/ijs.12294

DO - 10.1111/ijs.12294

M3 - Journal article

C2 - 24828363

VL - 9

SP - 642

EP - 645

JO - International Journal of Stroke

JF - International Journal of Stroke

SN - 1747-4930

IS - 5

ER -