Supervised Treadmill Exercise and Ranolazine for Intermittent Claudication of Lower Extremities (STERILE)

William Beaumont Hospitals

Status: Terminated

Conditions: Peripheral Arterial Disease

Treatments: Drug: Ranolazine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00914316

2009-051

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 29 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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29 participants in 4 patient groups, including a placebo group

Phase 1-Ranolazine, Phase 2-Ranolazine

Active Comparator group

Description:

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.

Treatment:

Drug: Ranolazine

Phase 1 -Ranolazine, Phase 2 -Placebo

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Ranolazine

Phase 1 -Placebo, Phase 2 -Ranolazine

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Ranolazine

Phase 1 -Placebo, Phase 2 -Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo