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| [ Print-friendly version ] |
| Efficacy of Nitric Oxide in Stroke |
| ISRCTN | ISRCTN99414122 |
| ClinicalTrials.gov identifier | |
| Public title | Efficacy of Nitric Oxide in Stroke |
| Scientific title | |
| Acronym | ENOS |
| Serial number at source | N/A |
| Study hypothesis |
Three-quarters of patients are hypertensive at the presentation of acute stroke while a high blood pressure is independently associated with a poor outcome. No large trials have specifically assessed whether blood pressure should be actively altered during the acute phase of stroke although outcome was worse in some trials of calcium channel blockers and beta receptor antagonists, probably through negative effects on cerebral blood perfusion and cardiac outout. However, small studies involving drugs from other antihypertensive classes, including nitric oxide donors, suggest they may reduce blood pressure without reducing cerebral blood flow. Similarly, no studies have assessed whether prior anti-hypertensive medication should be stopped or continued. A definitive trial is now required to:
1. Assess the balance of risk and benefit of lowering blood pressure immediately after ischaemic and haemorrhagic stroke. 2. Assess whether prior antihypertensive therapy should be continued or stopped temporarily after stroke. Further reading (added 28/01/10): 1. The NeuroGrid stroke exemplar clinical trial protocol. Wardlaw JM et al. International Journal of Stroke 2007;2:63-69 http://www.ncbi.nlm.nih.gov/pubmed/18705995 2. Effect of nitric oxide donors on blood pressure and pulse pressure in acute and subacute stroke. Gray LJ et al. International Journal of Stroke 2007;2:63-69 http://www.ncbi.nlm.nih.gov/pubmed/17904083 3. Management of blood pressure in acute stroke. Phillips at al. Canadian J Neurological Sciences 2002;29;404 http://www.ncbi.nlm.nih.gov/pubmed/12463498 4. ENOS Efficacy of Nitric Oxide in Stroke Trial. Stroke Center Stroke Trials Registry (2002) http://www.strokecenter.org/trials/TrialDetail.aspx?tid=103 Please note that as of 28/01/10 this record has been updated. All updates can be found in the relevant field with the above update date. In addition, the following countries of recruitment have been added; Egypt, India, Malaysia, Romania, Saudi Arabia, Spain, and Sri Lanka. Please note that as of 01/02/10 the end date of this trial has been extended from 31/10/11 to 31/10/13 |
| Lay summary | |
| Ethics approval |
Added 01/02/10:
Trent Regional Ethics Committee (REC) and the National Research Ethics Service (NRES) approved on the 3rd of September 2001 (ref: MREC/01/4/046) |
| Study design | Prospective international multicentre randomised parallel-group double-blind placebo-controlled trial |
| Countries of recruitment | Australia, Belgium, Canada, China, Egypt, Hong Kong, India, Italy, Malaysia, New Zealand, Philippines, Poland, Romania, Saudi Arabia, Singapore, Spain, Sri Lanka, United Kingdom |
| Disease/condition/study domain | Acute stroke |
| Participants - inclusion criteria | 5000 patients with acute ischaemic or haemorrhagic stroke within 48 hours, systolic blood pressure 140-220 mmHg |
| Participants - exclusion criteria |
1. Unconscious (Glasgow Coma Scale less than eight)
2. Definite need for nitrate therapy: concurrent myocardial infarction, unstable angina, left ventricular failure 3. Dehydration 4. Contraindication to nitrate therapy: hypersensitivity to nitrates, hypovolaemia, hypertrophic obstructive cardiomyopathy, aortic stenosis, cardiac tamponade, constrictive pericarditis, mitral stenosis, marked anaemia, closed-angle glaucoma, sildenafil (Viagra) within previous 24 hours 5. Systolic blood pressure less than 140 mmHg or more than 220 mmHg 6. Patients expected to require surgical intervention (e.g. clot evacuation, carotid endarterectomy) during the treatment or follow-up period 7. Refusal to consent 8. Patient dependent on others prior to stroke (e.g. Rankin score more than three) 9. Known intracerebral pathology other than ischaemic stroke, e.g. subarachnoid haemorrhage, brain tumour, cerebral abscess 10. Other serious condition which is likely to prevent outcome assessment, e.g. advanced cancer 11. Involvement in a trial of another experimental intervention (drug or surgery) for acute stroke 12. Not available for follow-up, e.g. no fixed address, overseas visitor 13. Females of childbearing potential, pregnancy or breastfeeding |
| Anticipated start date | 01/01/2004 |
| Anticipated end date | 31/10/2013 |
| Status of trial | Ongoing |
| Patient information material | |
| Target number of participants | 5000 |
| Interventions |
1. Glyceryl trinitrate (transdermal)
2. Continue/temporarily stop prior anti-hypertensive therapy |
| Primary outcome measure(s) | Death and dependency (Rankin score more than two). |
| Secondary outcome measure(s) |
1. Events by seven days - recurrent stroke, symptomatic deep vein thrombosis, symptomatic pulmonary embolism, blood pressure daily between 1 and 7 days
2. Hospital events - length of stay in hospital, discharge disposition (death, institution, or home) 3. Outcome at 90 days - Barthel Index (less than 60, including death), Barthel Index more than 95/100 at three months (good outcome), quality of life (EuroQol), abbreviated mental test score 4. Safety measures - death at 7 and 90 days, symptomatic intracranial haemorrhage at 7 days, major extracranial haemorrhage at 10 days |
| Sources of funding |
1. UK Medical Research Council: from 1 November 2006
2. Singapore A*STAR (MRI sub-study) 3. UK BUPA Foundation: 1 April 2004 - 31 October 2006 4. UK Medical Research Council (as part of NeuroGRID) 5. UK Hypertension Trust: 1 September 02 - 31 August 2004 6. UK Reichstadt bequest 7. UK Stroke Association 8. UK University of Nottingham (through Information Services) |
| Trial website | http://www.enos.ac.uk/ |
| Publications |
1. 2006 protocol in http://www.ncbi.nlm.nih.gov/pubmed/18706028
2. 2009 interim results in http://www.ncbi.nlm.nih.gov/pubmed/19106795 3. Conference proceedings: Continuing prior antihypertensive medication in acute stroke lowers blood pressure: Data from the continue vs stop arm of the 'Efficacy of Nitric Oxide in Stroke' (ENOS) trial. World Congress of Neurology, Sydney, November 2005 |
| Contact name | Prof Philip Bath |
| Address |
Division of Stroke
University of Nottingham City Hospital Campus |
| City/town | Nottingham |
| Zip/Postcode | NG5 1PB |
| Country | United Kingdom |
| Tel | +44 (0)115 823 1768 |
| Fax | +44 (0)115 823 1771 |
| enos@nottingham.ac.uk | |
| Sponsor | University of Nottingham (UK) |
| Address | University Park |
| City/town | Nottingham |
| Zip/Postcode | NG7 2RD |
| Country | United Kingdom |
| Sponsor website: | http://www.nottingham.ac.uk/SCS/Divisions/Stroke/index.aspx |
| Date applied | 12/11/2002 |
| Last edited | 01/02/2010 |
| Date ISRCTN assigned | 12/11/2002 |
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