Clinical trial NCT01833312: Cooling Plus Best Medical Treatment Versus Best Medical Treatment Alone for Acute Ischaemic Stroke
Official title: EuroHYP-1: European Multicentre, Randomised, Phase III Clinical Trial of Therapeutic Hypothermia Plus Best Medical Treatment Versus Best Medical Treatment Alone for Acute Ischaemic Stroke
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: acute ischemic stroke
hypothermia
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2013-04-16
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Participation in an interventional clinical trial within the last 4 weeks, or be under the exclusion period from another trial
* Prior participation in this trial
* Any acutely life-threatening conditions other than acute ischaemic stroke
* Rapidly resolving stroke symptoms
* Evidence from CT or MRI of intracranial haemorrhage or tumour or encephalitis or any diagnosis likely to cause the present symptoms other than acute ischaemic stroke. Haemorrhagic transformation of the infarct is not an exclusion criterion, except when there is a parenchymal haematoma covering more than 30% of the infarcted area, with significant space-occupying effect, or when there is a bleeding remote from the infarcted area
* 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)
* Severe cardiac failure, defined as NYHA classification ≥III
* Myocardial infarction or angina pectoris in the 3 months prior to screening
* Vasospastic disorders (e.g., Raynaud's disease)
* Haematological dyscrasia (e.g., sickle cell disease, cryoglobulinaemia)
* Known platelet count \<100,000/mm3
* Known INR \>1.7
* Skin damage (e.g., inflammation, burns, injuries, ulcerations, hives, rash) at the sites intended to be used for cooling
* Clinical diagnosis of sepsis
* Known severe hepatic impairment (serum ALAT and/or ASAT \>3 times ULN)
* Known renal impairment (serum creatinine \>2mg/100ml)
* Addison's disease
* Any other condition that may interfere with, or be aggravated by, therapeutic hypothermia
* Any condition that is thought to reduce the compliance to cooperate with the trial procedures

Primary outcomes:
measure: modified Rankin scale
timeFrame: 3 months
Secondary outcomes:
measure: Mortality
timeFrame: 3 months
measure: Neurological outcome
timeFrame: 3 months
measure: Quality of life
timeFrame: 3 months
measure: Cerebral infarct size
timeFrame: 48±24 hours
measure: Safety of systemic cooling
timeFrame: Enrollment - day 91
measure: Tolerability of systemic cooling
timeFrame: 36 hours
Other outcomes:
measure: Selected biomarkers
timeFrame: baseline, 24h, 72h
measure: Other imaging parameters
timeFrame: baseline, 48h
measure: Cost-effectiveness parameters
timeFrame: 3 months
Locations:
city: Erlangen
country: Germany
facility: Department of Neurology, University Hospital Erlangen
Study officials:
affiliation: University of Erlangen-Nürnberg
name: Stefan Schwab, Prof
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.