EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke

Int J Stroke. 2014 Jul;9(5):642-5. doi: 10.1111/ijs.12294. Epub 2014 May 15.


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 Identifier: NCT01833312.

Keywords: acute stroke therapy; clinical trial; hypothermia; ischemic stroke; treatment.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Anti-Anxiety Agents / therapeutic use
  • Brain Ischemia / therapy*
  • Buspirone / therapeutic use
  • Clinical Protocols*
  • Europe
  • Humans
  • Hypothermia, Induced / methods*
  • Logistic Models
  • Meperidine / therapeutic use
  • Molecular Sequence Data
  • Outcome Assessment, Health Care / methods
  • Patient Selection
  • Severity of Illness Index
  • Stroke / therapy*
  • Treatment Outcome


  • Analgesics, Opioid
  • Anti-Anxiety Agents
  • Meperidine
  • Buspirone

Associated data