Supervised Treadmill Exercise and Ranolazine for Intermittent Claudication of Lower Extremities

Study Overview
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Brief Summary
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The goal of this study is to evaluate whether supervised treadmill exercise combined with ranolazine 1000 mg twice daily provides an incremental benefit in absolute walking distance over supervised exercise alone in patients with stable claudication. Investigators also seek to determine if the administration of ranolazine provides a sustained benefit after the completion of a supervised exercise regimen. Lastly, investigators wish to determine whether both exercise and ranolazine improves peak oxygen consumption and anaerobic threshold in patients with stable claudication.

Detailed Description
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The treatment groups are: A. Group A will be randomized to a 12 week supervised exercise program and ranolazine, (Ranexa) 1000 mg orally, twice daily, by mouth. B. Group B will be randomized to a 12 week supervised exercise program and placebo. After the 12 week supervised exercise program, all participants will undergo a second randomization to ranolazine or placebo for an additional 12 weeks, during which independent walking will be encouraged. Both groups will participate in a two week lead-in period after each randomization of the trial, allowing for the stabilization of their medications and dosing of ranolazine. Medications such as cilostazol, calcium channel blockers and nitrates will be discontinued during the lead-in period, unless their use is for management for high blood pressure. Anti-platelet (blood thinner) medications will be continued throughout the trial.

Official Title
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Supervised Treadmill Exercise and Ranolazine for Intermittent Claudication of Lower Extremities. THE STERILE TRIAL.

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Drug: Ranolazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females greater than 40 years of age. Documented peripheral arterial disease Stable lower extremity intermittent claudication (Rutherford class 1-3) for 3 months. Exclusion Criteria: Critical limb ischemia (Rutherford class 4-6). Percutaneous or surgical lower extremity revascularization within last 12 months. Myocardial infarction within the last 6 months. cardiac surgery within the last 6 months. Unstable angina Stable chronic angina New York Heart Association Class II-IV heart failure Left ventricular ejection fraction less than or equal to 35% Venous thromboembolism within the last 6 months. Uncontrolled high blood pressure, defined as systolic blood pressure greater than or equal to 180 mmHg or diastolic blood pressure greater than or equal to 110 mmHg. Allergy to ranolazine. corrected QT interval (QTc) greater than or equal to 440 ms in males or 460 ms in females. Pregnant or nursing females. Chronic dialysis therapy. Significant liver impairment (defined as transaminases greater than or equal to 3 times the upper limit of normal) within the last 6 months. Concomitant use of Cytochrome P450-3A (CYP3A) inhibitors Concomitant use of CYP3A inducers QTc prolonging agents Orthopedic or neurologic disorders that prevent treadmill walking. Current participation in a structured exercise program.

Ages Eligible for Study
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Minimum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phase 1-Ranolazine, Phase 2-Ranolazine<br>This group will participate in the Phase 1 -12 week supervised exercise program and will additionally receive ranolazine 1000 mg orally, twice daily, by mouth. In Phase 2, the group will exercise independently and also receive ranolazine 1000 mg orally twice daily by mouth. | Drug: Ranolazine<br>* Ranolazine, 1000 mg, capsule, twice daily, by mouth.<br>* Other names: Ranexa;|
| Active Comparator: Phase 1 -Ranolazine, Phase 2 -Placebo<br>This group will participate in the Phase 1 -12 week supervised exercise program and will additionally receive ranolazine 1000 mg orally, twice daily, by mouth. In Phase 2, the group will exercise independently and will receive a sugar pill in place of the study drug. | Drug: Ranolazine<br>* Ranolazine, 1000 mg, capsule, twice daily, by mouth.<br>* Other names: Ranexa;Drug: Placebo<br>* twice daily<br>* Other names: sugar pill;|
| Active Comparator: Phase 1 -Placebo, Phase 2 -Ranolazine<br>This group will participate in the Phase 1 -12 week supervised exercise regimen and will receive a sugar pill in place of the study drug. In Phase 2, the group will exercise independently and also receive ranolazine 1000 mg orally twice daily by mouth. | Drug: Ranolazine<br>* Ranolazine, 1000 mg, capsule, twice daily, by mouth.<br>* Other names: Ranexa;Drug: Placebo<br>* twice daily<br>* Other names: sugar pill;|
| Placebo Comparator: Phase 1 -Placebo, Phase 2 -Placebo<br>This group will participate in the Phase 1 -12 week supervised exercise regimen and will receive a sugar pill in place of the study drug. In Phase 2, the group will exercise independently and will receive a sugar pill in place of the study drug. | Drug: Placebo<br>* twice daily<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Increase in Absolute Walking Distance Following Phase 1 | Change in absolute walking distance in meters from baseline to 12 week follow-up treadmill test, as a percentage from baseline treadmill test | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Increase in Absolute Walking Distance Following Phase 2 | Change in absolute walking distance in meters from baseline to 24 week follow-up treadmill test, as a percentage from baseline treadmill test | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lower leg claudication, Poor circulation of the leg muscles, Cramping or discomfort in the lower legs, Lower leg pain, PAD (Peripheral arterial disease)