PRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes

Study Overview
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Brief Summary
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The purpose of the trial is to determine if extended-release dipyridamole + aspirin [Aggrenox, Asasa ntin] is superior to clopidogrel [Plavix], and if telmisartan [Micardis, Gliosartan, Kinzal, Kinzalm ono, Predxal, Pritor, Samertan, Telmisartan] is superior to placebo, in the presence of background antihypertensive therapy, in prevention of a second stroke in patients who have recently suffered a stroke and therefore are at high risk of suffering another one.

Official Title
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PRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes: A Double-blind, Active and Placebo Controlled Study of Aggrenox vs. Clopidogrel, With and Without Micardis

Conditions
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Stroke

Intervention / Treatment
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* Drug: Aggrenox
* Drug: Aggrenox
* Drug: Clopidogrel placebo
* Drug: Clopidogrel placebo
* Drug: Micardis
* Drug: Micardis
* Drug: Aggrenox placebo
* Drug: Aggrenox placebo
* Drug: Clopidogrel
* Drug: Clopidogrel
* Drug: Micardis placebo
* Drug: Micardis placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female subjects 55 year or older who have suffered an ischemic stroke within the past 90 days and who meet all other inclusion criteria. Include also patients of ages 50 - 54 years and/or 90 to 120 days after the qualifying stroke provided the patient has at least two of the following additional risk factors: Diabetes mellitus Hypertension (systolic BP ¿ 140 or diastolic BP ¿ 90) Smoker at time of qualifying stroke Obesity (BMI>30; BMI=weight (kg)/[height (m)]2) Previous vascular disease (stroke, MI, or peripheral arterial disease prior to qualifying stroke) End-organ-damage (retinopathy, LVH, or microalbuminuria) Hyperlipidemia Exclusion criteria: hemorrhagic stroke (must be ruled out by imaging);unable to give informed consent; known brain tumor, severe renal or hepatic insufficiency, current active peptic ulcer disease, severe coronary artery disease including unstable angina pectoris or an MI within the previous 3 months,or history of a hemostatic disorder or systemic bleeding ;hyperkalemia;uncorrected volume or sodium depletion; pre-stroke history of dementia;modified Rankin score greater than 4;qualifying stroke induced by surgical or cardiovascular procedure;uncontrolled hypertension at entry above 180/110 mmHg (goal BPs are lower); SBP 120 mmHg or less for hospitalized patients; currently taking an ARB and not able or willing to switch to alternative; required or planned continuing treatment with antithrombotics or anticoagulants including heparin or warfarin or non-study platelet inhibitors; syndrome of asthma, rhinitis and nasal polyps;scheduled for major surgery, carotid endarterectomy, or carotid angioplasty (4 weeks post surgery is allowed);unlikely to be released from hospital following the qualifying stroke or presence of a severe disability likely to lead to being bedridden or demented or a non-vascular disease or condition which makes it unlikely that the patient will survive to the end of the trial; history of thrombocytopenia or neutropenia.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Aggrenox, Clopidogrel placebo, Micardis<br>Aggrenox (25mg/200mg) bid, clopidogrel placebo qd, Micardis (80mg) qd | Drug: Aggrenox<br>* 25mg aspirin, 200 mg dipyridamole<br>Drug: Clopidogrel placebo<br>* placebo<br>Drug: Micardis<br>* 80 mg micardis<br>|
| Placebo Comparator: Aggrenox placebo, clopidogrel,, Micardis<br>Clopidogrel (75mg) qd; Aggrenox placebo bid, Micardis (80mg) qd | Drug: Micardis<br>* 80 mg micardis<br>Drug: Aggrenox placebo<br>* placebo<br>Drug: Clopidogrel<br>* 75 mg clopidogrel<br>|
| Placebo Comparator: Aggrenox, clop placebo, micardis placebo<br>Aggrenox (25mg/200mg) bid, clopidogrel placebo qd, Micardis placebo qd | Drug: Aggrenox<br>* 25mg aspirin, 200 mg dipyridamole<br>Drug: Clopidogrel placebo<br>* placebo<br>Drug: Micardis placebo<br>* placebo<br>|
| Placebo Comparator: Aggrenox plcebo, clop, micardis placebo<br>Clopidogrel (75mg) qd, Aggrenox placebo bid, Micardis placebo qd. | Drug: Aggrenox placebo<br>* placebo<br>Drug: Clopidogrel<br>* 75 mg clopidogrel<br>Drug: Micardis placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Antiplatelet Comparison Only) |  | time since randomization; follow-up period is 1.5 to 4.4 years | 
| Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Telmisartan vs. Placebo Only) |  | time since randomization; follow-up period is 1.5 to 4.4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Outcome of Stroke, Myocardial Infarction (MI), or Vascular Death (Antiplatelet Comparison Only) | Number of patients with any of stroke, myocardial infarction, vascular death | time since randomization; follow-up period is 1.5 to 4.4 years | 
| Composite Outcome of Stroke, Myocardial Infarction, Vascular Death, or New or Worsening Congestive Heart Failure (CHF) (Telmisartan vs. Placebo Only) | Number of patients with any of stroke, myocardial infarction, vascular death, or new or worsening congestive heart failure | time since randomization; follow-up period is 1.5 to 4.4 years | 
| Number of Patients With New Onset of Diabetes (Telmisartan vs. Placebo Only) |  | Randomization to final patient contact |