The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial was a 2-by-2 factorial, double-blind, active and placebo-controlled study of the fixed combination of low-dose aspirin (25 mg) and extended-release dipyridamole (200 mg) given twice daily as compared with clopid ogrel (75 mg) given once daily, and of telmisartan (80 mg once daily) as compared with placebo, in patients with a recent ischemic stroke. This article focuses on the antiplatelet comparison within the factorial design. The antiplatelet part of the factorial design was initially intended to compare clopidogrel plus aspirin with aspirin plus extended-release dipyridamole. The design was modified, after 2027 patients were randomly assigned, when the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent TIA or Ischemic Stroke (MATCH) trial demonstrated an increased risk of bleeding with the combination of clopidogrel and aspirin.8 (link) Patients initially assigned to receive clopidogrel plus aspirin had been treated for up to 8 months before they were switched to clopidogrel alone at the time of the protocol amendment; 18,305 patients were subsequently randomly assigned to receive aspirin plus extended-release dipyridamole or clopidogrel alone.
Details of the trial design have been published previously.18 (link) The steering committee designed and oversaw the trial; data management was performed by the sponsor (Boehringer Ingelheim). A trial management committee, with representatives from the steering committee and the sponsor, met regularly to evaluate progress. The cochairs and the members of the steering committee had complete access to the trial data and prepared the final manuscript, and they vouch for the design, the final statistical analysis, and the completeness, accuracy, and interpretation of the data. The final statistical analyses were conducted simultaneously by the independent statisticians at the Medical University of South Carolina (who provided data and interim analysis reports to the data and safety monitoring committee) and the statisticians from Boehringer Ingelheim.
The protocol was approved by the appropriate regulatory authorities and ethics committees or institutional review boards. All patients provided written informed consent.
Details of the trial design have been published previously.18 (link) The steering committee designed and oversaw the trial; data management was performed by the sponsor (Boehringer Ingelheim). A trial management committee, with representatives from the steering committee and the sponsor, met regularly to evaluate progress. The cochairs and the members of the steering committee had complete access to the trial data and prepared the final manuscript, and they vouch for the design, the final statistical analysis, and the completeness, accuracy, and interpretation of the data. The final statistical analyses were conducted simultaneously by the independent statisticians at the Medical University of South Carolina (who provided data and interim analysis reports to the data and safety monitoring committee) and the statisticians from Boehringer Ingelheim.
The protocol was approved by the appropriate regulatory authorities and ethics committees or institutional review boards. All patients provided written informed consent.
