Trial Name: Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS)
Rationale: Survivors of ischemic stroke have a high risk of recurrent stroke and death. Following stroke, the highest recurrence rate is in the first 5 days after the event. The long-term recurrence rate is between 5% and 15% per year depending on the infarct subtype, vascular risk factors and concomitant diseases. PRoFESS will investigate the benefit and risk of a antiplatelet combination therapy in the early and long-term prevention of recurrent stroke. PRoFESS will also investigate the benefit of telmisartan, an ARB, versus placebo in the early phase after stroke and long-term treatment on top of usual antihypertensive therapy both in hypertensive and normotensive stroke patients. PRoFESS will be the largest stroke trial ever to investigate the prevention of recurrent stroke.
Design: PRoFESS is designed as a multicenter, randomised, double blind, double-dummy, active and placebo controlled, parallel group trial involving a 2x2 factorial design.
Sample Size: 15,500 ischemic stroke patients at up to 600 sites in 24 countries.
Population studied: Patients at least 55 years of age with an ischemic stroke who are neurologically and clinically stable. The qualifying stroke must be within 90 days of entry into the study with a target of 60% randomized within 10 days of stroke.
Interventions: Patients will be randomized to either of two antiplatelet combination regimens (low-dose aspirin plus extended-release dipyridamole vs the combination of clopidogrel plus 75mg aspirin) and randomisation to treatment with an ARB (telmisartan 80 mg) or placebo.
Outcome measures: The primary outcome for the trial is the time to any recurrent stroke (target of 2280 strokes). Secondary outcomes include time to recurrent stroke, MI, vascular death and hospitalisation due to congestive heart failure.
Statistical analysis: The treatments will be compared using a Cox survival model with terms for treatment group and age at entry, and stratified by Rankin Score. An independent Data and Saftey Monitoring Board will perform interim analyses.
Trial status: First patient randomized on September 11, 2003. Enrollment period is projected to be 2 years; total study duration is projected to be 4 years, based on the estimated time until 2280 strokes occur among randomized patients.
Principal investigators: RL Sacco, C Diener, S Yusuf
Sponsor: This large, unique trial is sponsored by Boehringer Ingelheim and is the product of an active academic-industrial collaboration.