Cooling Plus Best Medical Treatment Versus Best Medical Treatment Alone for Acute Ischaemic Stroke

NCT01833312 | Terminated Phase 3 DMC

• 1 other identifier: EuroHYP-1
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if systemic cooling to a target temperature of 34 to 35°C, started within 6 hours of symptom onset and maintained for 12 hours, improves functional outcome at 3 months in patients with acute ischaemic stroke.

Conditions

Acute Ischemic Stroke

Keywords

acute ischemic stroke; hypothermia

Outcome Measures

Primary Outcomes (1)

• modified Rankin scale

  Analysed with ordinal logistic regression and expressed as a common odds ratio.

  3 months

Secondary Outcomes (6)

• Mortality

  3 months

• Neurological outcome

  3 months

• Quality of life

  3 months

• Cerebral infarct size

  48±24 hours

• Safety of systemic cooling

  Enrollment - day 91

Other Outcomes (3)

• Selected biomarkers

  baseline, 24h, 72h

• Other imaging parameters

  baseline, 48h

• Cost-effectiveness parameters

  3 months

Study Arms (2)

Hypothermia

EXPERIMENTAL

Best medical treatment + hypothermia 34-35°C for 24h

Device: Hypothermia; Drug: Buspirone; Drug: Pethidine

Control

NO INTERVENTION

Best medical treatment

Interventions

Hypothermia DEVICE

In patients randomised to therapeutic hypothermia, induction of cooling will be started by infusion of 4°C isotone saline or Ringer's lactate administered over a period of 30 to 60 minutes. A body temperature between 34.0 and 35.0°C will be targeted. Body temperature will be monitored through bladder or rectal thermal probes, and cooling procedures will be adapted to keep body temperature as close as possible to the target. Maintenance of body temperature in the target range will be performed with a surface or endovascular cooling device. After a cooling period of 24h, controlled rewarming to 36°C with a rate of 0.2°C/h will be started. After 36°C have been reached, the device will be disconnected.

Also known as: EMCOOLS Brain.Pad, Arctic Sun and ArcticGel Pads, CritiCool and CureWrap 3500, Zoll intravascular temperature management system

Hypothermia

Buspirone DRUG

anti-shivering treatment

Hypothermia

Pethidine DRUG

anti-shivering treatment

Hypothermia

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained from the patient or his/her legally acceptable representative or under such other arrangements as may be legally established in participating countries
• Patients of both sexes aged ≥18 years
• Estimated body weight of 50 up to and including 120kg
• Diagnosis of acute ischaemic stroke
• Possibility to start therapeutic hypothermia within 6 hours after onset of stroke
• Possibility to start therapeutic hypothermia within 150 minutes after start of alteplase administration in patients receiving thrombolysis at the trial site or within 150 minutes after start of endovascular treatment, if this is later
• Possibility to start therapeutic hypothermia within 150 minutes after admission to trial site in patients not receiving thrombolysis or in patients who have received thrombolysis at a different site
• mRS score ≤2 prior to onset of stroke
• NIHSS score ≥6
• GCS motor response subscale score ≥5

You may not qualify if:

• Use of monoamineoxidase inhibitors in the 14 days prior to screening
• Current use of medication interacting with pethidine or buspirone, i.e., ritonavir, phenytoin, cimetidine, phenothiazines, opioids and partial opioid agonists (e.g., pentazocine, nalbuphine, buprenorphine)
• Acute alcohol intoxication
• Opioid addiction
• Nursing mother or pregnant woman, as verified by a positive urine pregnancy test in females of childbearing potential
• Known hypersensitivity to the IMPs or any of their formulation ingredients
• Patient who is imprisoned or is lawfully kept in an institution
• Employee or direct relative of an employee of the CRO (if applicable), the department of the investigator, or the sponsor
• Prior participation in this trial
• Any acutely life-threatening conditions other than acute ischaemic stroke
• Rapidly resolving stroke symptoms
• Known convulsive disorder, acute closed angle glaucoma, myasthenia gravis
• SPO2 \<94% (as measured by pulse oximetry) under nasal oxygen administration
• Other severe respiratory disorder
• Bradycardia (\<40 bpm)

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Department of Neurology, University Hospital Erlangen

Erlangen, 91054, Germany

Location

Related Publications (2)

• Winkel P, Bath PM, Gluud C, Lindschou J, van der Worp HB, Macleod MR, Szabo I, Durand-Zaleski I, Schwab S; EuroHYP-1 trial investigators. Statistical analysis plan for the EuroHYP-1 trial: European multicentre, randomised, phase III clinical trial of the therapeutic hypothermia plus best medical treatment versus best medical treatment alone for acute ischaemic stroke. Trials. 2017 Nov 29;18(1):573. doi: 10.1186/s13063-017-2302-z.

  PMID: 29187242 DERIVED

• van der Worp HB, Macleod MR, Bath PM, Demotes J, Durand-Zaleski I, Gebhardt B, Gluud C, Kollmar R, Krieger DW, Lees KR, Molina C, Montaner J, Roine RO, Petersson J, Staykov D, Szabo I, Wardlaw JM, Schwab S; EuroHYP-1 investigators. 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.

  PMID: 24828363 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Hypothermia

Interventions

Buspirone; Meperidine

Condition Hierarchy (Ancestors)

Stroke; 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)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds; Isonipecotic Acids; Acids, Heterocyclic; Piperidines

Study Officials

• Stefan Schwab, Prof

  University of Erlangen-Nürnberg

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: April 16, 2013
• Study Start: July 1, 2013
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: October 2, 2019

Record last verified: 2019-09

Locations

DE (1)