Improving the management of blood pressure in acute stroke: the Efficacy of Nitric Oxide in Stroke (ENOS) trial
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Medical & Surgical Sciences
Abstract
The Efficacy of Nitric Oxide in Stroke (ENOS) Trial examines treating high blood pressure within 48 hours of stroke. Many patients have high blood pressure immediately after a stroke and we know that these people are more likely to die or be disabled than patients with normal blood pressure. At present, doctors do not usually treat high blood pressure immediately after a stroke so this trial investigates whether or not lowering blood pressure helps people to recover.
We are using a well-established medication called glyceryl trinitrate (GTN) which relaxes blood vessels to lower blood pressure. The trial will recruit 5,000 patients and compares patients treated with GTN for 7 days against patients who do not receive GTN. The trial also examines whether or not patients blood pressure treatment should stop or continue for 7 days. Patients are followed up by telephone call at 90 days. The main outcome is comparison of the number of patients who have died or are too disabled to care for themselves after their stroke.
ENOS is an international trial with 52 current centres recruiting patients across 13 countries. The trial is funded by the MRC until November 2011. The University of Nottingham is the sponsor.
We are using a well-established medication called glyceryl trinitrate (GTN) which relaxes blood vessels to lower blood pressure. The trial will recruit 5,000 patients and compares patients treated with GTN for 7 days against patients who do not receive GTN. The trial also examines whether or not patients blood pressure treatment should stop or continue for 7 days. Patients are followed up by telephone call at 90 days. The main outcome is comparison of the number of patients who have died or are too disabled to care for themselves after their stroke.
ENOS is an international trial with 52 current centres recruiting patients across 13 countries. The trial is funded by the MRC until November 2011. The University of Nottingham is the sponsor.
Technical Summary
High blood pressure (BP 140+/90+ mmHg) affects 75+% of patients presenting with acute stroke and is independently associated with a poor outcome (increased death or dependency) and early recurrence. Lowering a high BP could improve outcome providing cerebral blood flow is not reduced. Additionally, about 50% of patients are taking antihypertensive treatment prior to their stroke but it remains unclear whether this should be continued or stopped temporarily. Our Cochrane ?Blood pressure in Acute Stroke Collaboration? review identified no completed large trials assessing these questions.
We have developed a way of lowering BP with transdermal glyceryl trinitrate (GTN, as used in patients with angina) in three small randomised controlled trials (total 145 patients) in acute/sub-acute stroke. GTN lowered BP in a controlled manner without altering cerebral blood flow or platelet function, allowed patients who were unable to swallow to be treated, was easy to administer, and appeared to be safe.
The start-up phase (395 patients recruited as at 26/09/05) of the ?Efficacy of Nitric Oxide in Stroke? (ENOS) trial is investigating the effects of GTN (5 mg daily for 7 days) versus control on safety (death, deterioration, recurrence), BP, and CT lesion size and swelling, in an international single-blind randomised controlled trial involving hypertensive patients with acute (within 48 hours) ischaemic or haemorrhagic stroke. The trial is also addressing whether prior antihypertensive therapy should be continued or stopped temporarily in relevant individuals. ENOS is the first acute stroke trial to use the internet for randomisation, data registration, and adjudication of CT scans/serious adverse events. Interim 6 monthly reviews by the Data Monitoring Committee have not identified hazard and have recommended that ENOS should continue. We now seek funding from the MRC to recruit 4600 patients (total 5000) into the main trial phase over 5 years starting April 2006. The trial will assess the effect of these interventions on functional outcome (modified Rankin Scale, primary outcome) as well as recurrence, cognition, mood and quality-of-life. Subgroup analyses will assess the interventions by stroke type, clinical syndrome, baseline BP, severity, time to randomisation, and presence of infarct swelling on CT.
Transdermal GTN is readily available, easy to administer and monitor, inexpensive (#5 per patient) and could be relevant to most patients with acute stroke. A positive large trial would benefit patients and society, reduce load on carers and health care, and contribute to the UK Government?s health strategy.
We have developed a way of lowering BP with transdermal glyceryl trinitrate (GTN, as used in patients with angina) in three small randomised controlled trials (total 145 patients) in acute/sub-acute stroke. GTN lowered BP in a controlled manner without altering cerebral blood flow or platelet function, allowed patients who were unable to swallow to be treated, was easy to administer, and appeared to be safe.
The start-up phase (395 patients recruited as at 26/09/05) of the ?Efficacy of Nitric Oxide in Stroke? (ENOS) trial is investigating the effects of GTN (5 mg daily for 7 days) versus control on safety (death, deterioration, recurrence), BP, and CT lesion size and swelling, in an international single-blind randomised controlled trial involving hypertensive patients with acute (within 48 hours) ischaemic or haemorrhagic stroke. The trial is also addressing whether prior antihypertensive therapy should be continued or stopped temporarily in relevant individuals. ENOS is the first acute stroke trial to use the internet for randomisation, data registration, and adjudication of CT scans/serious adverse events. Interim 6 monthly reviews by the Data Monitoring Committee have not identified hazard and have recommended that ENOS should continue. We now seek funding from the MRC to recruit 4600 patients (total 5000) into the main trial phase over 5 years starting April 2006. The trial will assess the effect of these interventions on functional outcome (modified Rankin Scale, primary outcome) as well as recurrence, cognition, mood and quality-of-life. Subgroup analyses will assess the interventions by stroke type, clinical syndrome, baseline BP, severity, time to randomisation, and presence of infarct swelling on CT.
Transdermal GTN is readily available, easy to administer and monitor, inexpensive (#5 per patient) and could be relevant to most patients with acute stroke. A positive large trial would benefit patients and society, reduce load on carers and health care, and contribute to the UK Government?s health strategy.
