Cooling Plus Best Medical Treatment Versus Best Medical Treatment Alone for Acute Ischaemic Stroke (EuroHYP-1)
|Acute Ischemic Stroke||Device: Hypothermia Drug: Buspirone Drug: Pethidine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- modified Rankin scale [ Time Frame: 3 months ]Analysed with ordinal logistic regression and expressed as a common odds ratio.
- Mortality [ Time Frame: 3 months ]
- Neurological outcome [ Time Frame: 3 months ]
World Health Organization Disability Assessment Schedule (WHODAS) 2.0
- Quality of life [ Time Frame: 3 months ]EuroQoL 5-dimensions 5-level questionnaire
- Cerebral infarct size [ Time Frame: 48±24 hours ]Evaluated on CT or MRI imaging
- Safety of systemic cooling [ Time Frame: Enrollment - day 91 ]
Number of adverse events and severe adverse events related to the procedure of systemic cooling including induction, maintenance of hypothermia, rewarming, or the administration of anti-shivering medication (pethidine and buspirone) within the first 36h of enrollment.
Number of adverse events and severe adverse events until outcome assessment at day 91.
- Tolerability of systemic cooling [ Time Frame: 36 hours ]
Timing and dose of anti-shivering medication.
Bedside shivering assessment scale (BSAS).
- Selected biomarkers [ Time Frame: baseline, 24h, 72h ]
- MMPs including gelatinases (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8 and MMP-13) and stromelysins (MMP-3 and MMP-10) using multiplex ELISA [SearchLight technology].
- MMP endogen inhibitors (TIMP-1 and TIMP-2) using multiplex ELISA [SearchLight technology].
- H-FABP, UFD-1, RNABP, NDKA, GSTP-1 and Pro-BNP using standard ELISA.
- Cerebral Array I & II containing BDNF, GFAP, NSE, NGAL, sTNFRI, D-dimer and CRP using biochip analysers [Randox].
- Pro-ANP, Copeptin, IL6, IL8, IL10, mannose-binding lectin (MBL), mHLA-DR, monocytotic cytokine-secretion ex vivo stimulation, C5a in plasma, ultrasensitive PCT, lipopolysaccharide-binding protein (LBP).
- Other imaging parameters [ Time Frame: baseline, 48h ]Presence, location and extent of any visible infarct, early infarct swelling, hyperdense artery, leukoaraiosis, atrophy and prior infarct on the scan performed at screening assessment (within 90 minutes before the start of the treatment) will be tested for any interaction with early (infarct swelling, haemorrhagic transformation, neurological deterioration, death) and late (NIHSS and mRS scores, death) neurological and functional outcome variables at day 8 or day of discharge from hospital, whichever occurs firs, and at outcome assessment (day 91±14).
- Cost-effectiveness parameters [ Time Frame: 3 months ]
Patient location during stay in hospital.
Destination after discharge from hospital.
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||June 2020 (Final data collection date for primary outcome measure)|
Best medical treatment + hypothermia 34-35°C for 24h
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.
Other Names:Drug: Buspirone
anti-shivering treatmentDrug: Pethidine
No Intervention: Control
Best medical treatment
Please refer to this study by its ClinicalTrials.gov identifier: NCT01833312
|Contact: Stefan Schwab, Prof. Dr.||+email@example.com|
|Contact: Bernd Kallmuenzer, Drfirstname.lastname@example.org|
|Department of Neurology, University Hospital Erlangen||Recruiting|
|Erlangen, Germany, 91054|
|Contact: Dimitre Staykov, PD Dr. +4991318533001 email@example.com|
|Study Chair:||Stefan Schwab, Prof||University of Erlangen-Nürnberg|