EuroHYP-1: European phase III clinical trial at multiple trial sites and with random allocation of patients to treatment groups. The trial compares whole body cooling plus best medical treatment to best medical treatment alone in patients with acute stroke.

Phase 1

• Conditions: Acute ischaemic stroke; MedDRA version: 18.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2012-002944-25-IT
• Lead Sponsor: IVERSITY HOSPITAL ERLANGE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-09
• Study Completion: 2018-05-09
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

The trial population consists of patients of both sexes, aged =18 years, with acute ischaemic stroke and a score on the NIHSS of 6 up to and including 18 at screening [Assessment 1, within 90 minutes before the start of the treatment phase TP].

- 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.

- Estimated body weight of 50kg up to and including 120kg.

- 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.

- GCS motor response subscale score =5.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 750
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 750

Exclusion Criteria

1. Use of monoaminoxidase inhibitors in the 14 days prior to screening.
2. Current use of medication interacting with pethidine or buspirone.
3. Acute alcohol intoxication.
4. Opioid addiction.
5. Nursing mother or pregnant woman, as verified by a positive urine pregnancy test in females of childbearing potential.
6. Known hypersensitivity to the IMPs or any of their formulation ingredients.
7. Patient who is imprisoned or is lawfully kept in an institution.
8. Employee or direct relative of an employee of the CRO (if applicable), the department of the investigator, or the sponsor.
9. Participation in an interventional clinical trial within the last 4 weeks, or be under the exclusion period from another trial.
10. Prior participation in this trial.
11. Any acutely life-threatening conditions other than acute ischaemic stroke.
12. Rapidly resolving stroke symptoms.
13. 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.
14. Known convulsive disorder, acute closed angle glaucoma, myasthenia gravis.
15. SPO2 <94% (as measured by pulse oximetry) under nasal oxygen administration.
16. Other severe respiratory disorder.
17. Bradycardia (<40 bpm).
18. Severe cardiac failure, defined as NYHA classification =III.
19. Myocardial infarction or angina pectoris in the 3 months prior to screening.
20. Vasospastic disorders.
21. Haematological dyscrasia (e.g., sickle cell disease, cryoglobulinaemia).
22. Known platelet count <100,000/mm3.
23. Known INR >1.7.
24. Skin damage at the sites intended to be used for cooling.
25. Clinical diagnosis of sepsis.
26. Known severe hepatic impairment (serum ALAT and/or ASAT >3 times ULN).
27. Known renal impairment (serum creatinine >2mg/100ml).
28. Addison's disease.
29. Any other condition that may interfere with, or be aggravated by, therapeutic hypothermia.
30. Any condition that is thought to reduce the compliance to cooperate with the trial procedures

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether systemic cooling to a target body temperature between 34.0 and 35.0°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.;Secondary Objective: - To assess the effect of systemic cooling to a target body temperature between 34.0 and 35.0°C, started within 6 hours of symptom onset and maintained for 24 hours, in patients with acute ischaemic stroke on<br>• mortality at 3 months.<br>• neurological outcome at 3 months.<br>• quality of life at 3 months.<br>• cerebral infarct size at 48±24 hours.<br><br>- To determine the safety and tolerability of systemic cooling in patients with acute ischaemic stroke.;Primary end point(s): 1 Score on the mRS;Timepoint(s) of evaluation of this end point: At outcome assessment [A7, Day 91±14 days].

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1 Death or dependency, defined as a score on the mRS >2.<br>2 Death<br>3 Score on NIHSS.<br>4 Brain infarct size.<br>5 WHODAS 2.0 score<br>6 EQ-5D-5L score<br>;Timepoint(s) of evaluation of this end point: 1Death or dependency, defined as a score on the mRS >2 at outcome assessment [A7, Day 91±14 days].<br>2Death at outcome assessment [A7, Day 91±14 days]<br>3Score on NIHSS at outcome assessment [A7, Day 91±14 days].<br>4Brain infarct size at imaging assessment [A4, Hour 48±24 hours].<br>5WHODAS 2.0 score at outcome assessment [A7, Day 91±14 days].<br>6EQ-5D-5L score at outcome assessment [A7, Day 91±14 days].