Cooling Plus Best Medical Treatment Versus Best Medical Treatment Alone for Acute Ischaemic Stroke (EuroHYP-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Erlangen-Nürnberg Medical School
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT01833312
First received: April 4, 2013
Last updated: July 31, 2013
Last verified: July 2013
  Purpose

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 24 hours, improves functional outcome at 3 months in patients with acute ischaemic stroke.


Condition Intervention Phase
Acute Ischemic Stroke
Device: Hypothermia
Drug: Buspirone
Drug: Pethidine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

Primary Outcome Measures:
  • modified Rankin scale [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Analysed with ordinal logistic regression and expressed as a common odds ratio.


Secondary Outcome Measures:
  • Mortality [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Neurological outcome [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    NIHSS;

    World Health Organization Disability Assessment Schedule (WHODAS) 2.0


  • Quality of life [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    EuroQoL 5-dimensions 5-level questionnaire

  • Cerebral infarct size [ Time Frame: 48±24 hours ] [ Designated as safety issue: No ]
    Evaluated on CT or MRI imaging

  • Safety of systemic cooling [ Time Frame: Enrollment - day 91 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]

    Timing and dose of anti-shivering medication.

    Bedside shivering assessment scale (BSAS).



Other Outcome Measures:
  • Selected biomarkers [ Time Frame: baseline, 24h, 72h ] [ Designated as safety issue: No ]
    • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    Patient location during stay in hospital.

    Destination after discharge from hospital.



Estimated Enrollment: 1500
Study Start Date: July 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypothermia
Best medical treatment + hypothermia 34-35°C for 24h
Device: Hypothermia
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:
  • EMCOOLS Brain.Pad
  • Arctic Sun and ArcticGel Pads
  • CritiCool and CureWrap 3500
  • Zoll intravascular temperature management system
Drug: Buspirone
anti-shivering treatment
Drug: Pethidine
anti-shivering treatment
No Intervention: Control
Best medical treatment

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 90 minutes after start of alteplase administration in patients receiving thrombolysis
  • Possibility to start therapeutic hypothermia within 90 minutes after admission to trial site in patients not receiving thrombolysis
  • mRS score ≤2 prior to onset of stroke
  • NIHSS score of 6 up to and including 18
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01833312

Contacts
Contact: Stefan Schwab, Prof. Dr. +49-9131-8534563 direktion-neurologie@uk-erlangen.de
Contact: Dimitre Staykov, Priv.Doz Dr +49-9131-8544539 dimitre.staykov@uk-erlangen.de

Locations
Germany
Department of Neurology, University Hospital Erlangen Recruiting
Erlangen, Germany, 91054
Contact: Dimitre Staykov, PD Dr.    +4991318533001    dimitre.staykov@uk-erlangen.de   
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Investigators
Study Chair: Stefan Schwab, Prof University of Erlangen-Nuremberg
  More Information

No publications provided by University of Erlangen-Nürnberg Medical School

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT01833312     History of Changes
Other Study ID Numbers: EuroHYP-1
Study First Received: April 4, 2013
Last Updated: July 31, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Erlangen-Nürnberg Medical School:
acute ischemic stroke
hypothermia

Additional relevant MeSH terms:
Therapeutic Uses
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Buspirone
Meperidine
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on July 31, 2014