E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Acute stroke without bleeding in the brain. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061256 |
E.1.2 | Term | Ischaemic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 12 hours, improves functional outcome at 3 months in patients with acute ischaemic stroke. |
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E.2.2 | Secondary objectives of the trial |
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 12 hours, in patients with acute ischaemic stroke on • mortality at 3 months. • neurological outcome at 3 months. • quality of life at 3 months. • cerebral infarct size at 48±24 hours. To determine the safety and tolerability of systemic cooling in patients with acute ischaemic stroke. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 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 90 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. - GCS motor response subscale score ≥5. |
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E.4 | Principal exclusion criteria |
1.Current use of medication interacting with pethidine or buspirone. 2. Use of monoaminoxidase inhibitors in the 14 days prior to screening. 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 . |
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E.5 End points |
E.5.1 | Primary end point(s) |
Handicap score on the Modified Rankin Scale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At outcome assessment [A7, Day 91±14 days].
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E.5.2 | Secondary end point(s) |
-Death or dependency, defined as a score on the mRS >2. -Death. - Score on NIHSS. - Brain infarct size. - WHODAS 2.0 score. - EQ-5D-5L score. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Death or dependency, defined as a score on the mRS >2 at outcome assessment [A7, Day 91±14 days]. - Death at outcome assessment [A7, Day 91±14 days]. - Score on NIHSS at outcome assessment [A7, Day 91±14 days]. - Brain infarct size at imaging assessment [A4, Hour 48±24 hours]. - WHODAS 2.0 score at outcome assessment [A7, Day 91±14 days]. - EQ-5D-5L score at outcome assessment [A7, Day 91±14 days]. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |