A prospective, collaborative, international, multicentre, randomised, parallel-group, single and outcome blinded, controlled, factorial trial to investigate the safety and efficacy of treatment with transdermal glyceryl trinitrate, a nitric oxide donor, and of continuing or stopping temporarily pre-stroke antihypertensive therapy, in patients with acute stroke

Phase 1

• Conditions: Acute stroke; MedDRA version: 14.1Level: LLTClassification code 10042244Term: StrokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: PTClassification code 10014498Term: Embolic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: LLTClassification code 10057613Term: Thromboembolic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: LLTClassification code 10055221Term: Ischemic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: LLTClassification code 10067816Term: Cardioembolic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: LLTClassification code 10027580Term: Middle cerebral artery strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: LLTClassification code 10023027Term: Ischaemic stroke NOSSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 14.1Level: PTClassification code 10043647Term: Thrombotic strokeSystem Organ Class: 10029205 - Nervous system disorders

• Registration Number: EUCTR2004-003870-27-DK
• Lead Sponsor: niversity of Nottingham, Research Innovation Services

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-15
• Last Update Posted: 5 September 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 5000

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).
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: E.2.1Assess the balance of risk and benefit of lowering blood pressure with GTN immediately after ischaemic and haemorrhagic stroke.;Secondary Objective: Assess whether pre-stroke antihypertensive therapy should be continued or stopped temporarily after stroke;Primary end point(s): Combined death or dependency (modified Rankin Score >2)