E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | Stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014498 |
E.1.2 | Term | Embolic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057613 |
E.1.2 | Term | Thromboembolic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067816 |
E.1.2 | Term | Cardioembolic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027580 |
E.1.2 | Term | Middle cerebral artery stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023027 |
E.1.2 | Term | Ischaemic stroke NOS |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043647 |
E.1.2 | Term | Thrombotic 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 |
E.2.1 Assess the balance of risk and benefit of lowering blood pressure with GTN immediately after ischaemic and haemorrhagic stroke. |
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E.2.2 | Secondary objectives of the trial |
Assess whether pre-stroke antihypertensive therapy should be continued or stopped temporarily after stroke |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Genetic sub-study: An important aim of the genetic analyses is to determine whether polymorphic differences in candidate genes explain blood pressure and outcome responses to GTN (pharmacogenetic analysis). The exact genetic analyses to be performed are undefined at present and will depend on relevant scientific information available at the time of laboratory analysis and prior to sample destruction. Likely analyses will include genes related to the synthesis and metabolism of nitric oxide (e.g. endothelial nitric oxide synthase) and the mechanism of action of antihypertensive agents (e.g. polymorphisms in receptors) |
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E.3 | Principal inclusion criteria |
a) Adult (age > 18 years).b) Clinical stroke syndrome with limb weakness lasting at least 1 hour (i.e. not likely to be atransient ischaemic attack).c) Residual limb weakness at the time of enrolment (SSS Arm <6 and/or Leg <6, appendix C).d) Onset < 48 hours. If the time of onset is unknown, apply the time when the patient was lastknown to be well. [This timeframe covers the period of maximum uncertainty over alteringblood pressure and should permit the vast majority of otherwise eligible patients to berecruited]e) Conscious (Glasgow Coma Scale > 8).f) Systolic blood pressure in range 140 mmHg to 220 mmHg inclusive on the basis of at leastone of the three baseline pre-randomisation measures.g) Independent prior to stroke (pre-morbid modified Rankin Scale < 2).h) Meaningful consent, or assent from a relative or carer if the patient is unable to givemeaningful consent (e.g. in cases of dysphasia, confusion, or reduced conscious level). |
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E.4 | Principal exclusion criteria |
a) Definite need for nitrate therapy: e.g. concurrent myocardial infarction, unstable angina, leftventricular failure. Patients admitted on nitrates for the management of stable angina maystop these for the 7 day trial treatment period. b) Contraindication to nitrate therapy: e.g. hypersensitivity to nitrates, dehydration,hypovolaemia, hypertrophic obstructive cardiomyopathy, aortic stenosis, cardiactamponade, constrictive pericarditis, mitral stenosis, marked anaemia, closed-angleglaucoma, sildenafil (Viagra) or related drug, within 24 hours.c) Definite need for pre-stroke antihypertensive, anti-anginal or anti-heart failure medication:e.g. concurrent angina, heart failure.d) Definite need for new antihypertensive, anti-anginal or anti-heart failure medication duringacute stroke: e.g. concurrent angina, heart failure, hypertensive encephalopathy, aorticdissection.e) Patients expected, on the basis of existing investigations, to require surgical intervention(e.g. clot evacuation, carotid endarterectomy) during the treatment or follow-up period.) Known intracerebral pathology other than stroke, e.g. subarachnoid haemorrhage, braintumour, cerebral abscess.g) Other serious condition which is likely to prevent outcome assessment at 90 days, e.g.advanced cancer.h) Previous enrolment in ENOS.i) Current involvement in another trial of an experimental drug. [Patients may be randomisedinto observational studies or non-drug trials.]j) Not available for follow-up, e.g. no fixed address, overseas visitor.k) Females of childbearing potential where pregnancy cannot be excluded by a negativepregnancy test, pregnancy, or breastfeeding.l) Need for new antihypertensive therapy to lower systolic blood pressure to achieve theenrolment range of 140-220mmHgm) New (not prescribed pre-stroke) antihypertensive medication commenced after stroke onset |
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E.5 End points |
E.5.1 | Primary end point(s) |
Combined death or dependency (modified Rankin Score >2) |
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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 | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
E.8.1.3 | Single blind | Yes |
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 |
patch or no patch under gauze dressing |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |