Glyceryl trinitrate vs. control, and continuing vs. stopping temporarily prior antihypertensive therapy, in acute stroke: rationale and design of the Efficacy of Nitric Oxide in Stroke (ENOS) trial (ISRCTN99414122).
ENOS Trial Investigators None.
High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Many patients with acute stroke are taking antihypertensive medications. To test the safety and efficacy of 7 days of transdermal glyceryl trinitrate (GTN, 5 mg/day) vs. no GTN in patients with acute stroke; patients taking antihypertensive therapy immediately before their stroke are also randomised to continue vs. stop this temporarily. ENOS is a prospective international multicentre single-blind randomised-controlled trial in 5000 patients with acute (<48 h of onset) ischaemic or haemorrhagic stroke. The primary outcome is combined death and dependency (modified Rankin scale >2) at 90 days measured by blinded central telephone follow-up. Secondary outcomes include: BP over the 7 days of treatment; death, impairment (Scandinavian stroke scale), recurrence, and neuroimaging at 7 days; discharge disposition, disability (Barthel index), cognition (mini-mental status examination) and quality of life (EuroQoL). The sample size will allow an absolute difference in death/dependency of 5% to be detected with 90% power at 5% significance for GTN versus no GTN. Randomisation and data collection are performed over a secure Internet site with real-time data validation. Neuroimaging and serious adverse events are adjudicated blinded to treatment.