Ranolazine Versus Placebo Effects on Exercise Tolerance in Patients With Heart Disease and Peripheral Arterial Disease

Colorado Prevention Center Clinical Research

Status and phase

Withdrawn

Phase 4

Conditions

Peripheral Arterial Disease

Angina

Treatments

Drug: Placebo

Drug: Ranolazine

Study type

Interventional

Funder types

Other

Identifiers

NCT00657514

07-PAD-01

Details and patient eligibility

About

After 6 weeks of maximal Ranolazine therapy, tissue hemoglobin desaturation kinetics will change compared to placebo in patients with chronic angina and peripheral arterial disease.

Full description

Study Endpoints:

Primary Endpoint:

• The primary endpoint of this study is the change in the kinetics of tissue hemoglobin oxygen desaturation (expressed as time constants) following the onset of exercise.

Secondary endpoints of this study include percent and absolute change in:

Peak oxygen consumption
Pulmonary oxygen uptake on-kinetics
Steady state level of tissue hemoglobin desaturation during exercise
Recovery kinetics of tissue oxygen saturation following exercise

Adverse events will be collected.

Exploratory Endpoints

Peak Walking Time (PWT)
Claudication Onset Time (COT)
Time to Onset of Angina (TOA)

Study Design:

Investigator-initiated, prospective, randomized, double-blind, placebo-controlled study.

Inclusion Criteria:

Males age > 40 years.
Subjects must have chronic stable angina, meeting the labeled indications for ranolazine:

• Ranolazine is indicated for the treatment of chronic angina. Ranolazine should be reserved for subjects who have not achieved an adequate response with other anti-anginal drugs.
Subjects must have a resting ankle brachial index (ABI) of < 0.90 with a post-exercise decrement of ≥ 10% in at least one leg, OR a resting ABI of ≥0.90 to ≤ 1.00 with a post-exercise decrement of ≥ 20% in at least one leg
The subject has provided written informed consent to participate, understands the requirements of the study, and agrees to return for the required assessments

Exclusion Criteria:

Non-atherosclerotic diseases of the peripheral circulation by clinical history
Unable to complete the first stage of the modified, extended Astrand treadmill protocol
Clinically significant ECG abnormalities or changes with exercise on the screening ECG
Evidence of critical limb ischemia (CLI)
Hepatic impairment (Child-Pugh Classes A [mild], B [moderate], or C [severe])
End stage renal disease requiring dialysis
Hemoglobin < 12 mg/dL.
Platelet count < 90,000/mL.
Planned surgical/endovascular intervention for coronary artery disease (CAD) or peripheral arterial disease (PAD) in the next 3 months
Maximal exercise is limited by symptoms other than claudication or angina
Significant mental illness or drug abuse within 30 days of enrollment that in the opinion of the Investigator could impact the subject's ability to successfully complete the trial
Known allergy to ranolazine
Pre-existing QTc prolongation on a resting electrocardiogram (ECG) at Screening due to the risk of worsening of this condition with the use of ranolazine
Treatment with QT prolonging drugs such as Class IA (e.g. quinidine) and Class III (e.g. sotalol, dofetilide), antiarrhythmics, amiodarone, and antipsychotics (e.g. thioridazine, ziprasidone)
Treatment with potent or moderately potent CYP3A inhibitors including ketoconazole and other azole antifungals, diltiazem, verapamil, macrolide antibiotics, cyclosporine, rifampin or structurally related rifabutin and rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's Wort, or human immunodeficiency virus (HIV) protease inhibitors
The subject has previously received ranolazine within the 6-months prior to enrollment
The subject has received an investigational drug within 90 days prior to enrollment
Type 1 or type 2 diabetes mellitus
Congestive Heart Failure, ≥ New York Heart Association (NYHA) Class III
History of oxygen dependent Chronic Obstructive Pulmonary Disease (COPD)
Body Mass Index (BMI) >35

Sex

Male

Ages

40+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Males age > 40 years.
Subjects must have chronic stable angina, meeting the labeled indications for ranolazine:

Ranolazine is indicated for the treatment of chronic angina. Ranolazine should be reserved for subjects who have not achieved an adequate response with other anti-anginal drugs.

Subjects must have a resting ankle brachial index (ABI) of < 0.90 with a post-exercise decrement of ≥ 10% in at least one leg, OR a resting ABI of ≥0.90 to ≤ 1.00 with a post-exercise decrement of ≥ 20% in at least one leg
The subject has provided written informed consent to participate, understands the requirements of the study, and agrees to return for the required assessments

Exclusion criteria

Non-atherosclerotic diseases of the peripheral circulation by clinical history
Unable to complete the first stage of the modified, extended Astrand treadmill protocol
Clinically significant ECG abnormalities or changes with exercise on the screening ECG
Evidence of critical limb ischemia (CLI)
Hepatic impairment (Child-Pugh Classes A [mild], B [moderate], or C [severe])
End stage renal disease requiring dialysis
Hemoglobin < 12 mg/dL.
Platelet count < 90,000/mL.
Planned surgical/endovascular intervention for coronary artery disease (CAD) or peripheral arterial disease (PAD) in the next 3 months
Maximal exercise is limited by symptoms other than claudication or angina
Significant mental illness or drug abuse within 30 days of enrollment that in the opinion of the Investigator could impact the subject's ability to successfully complete the trial
Known allergy to ranolazine
Pre-existing QTc prolongation on a resting electrocardiogram (ECG) at Screening due to the risk of worsening of this condition with the use of ranolazine
Treatment with QT prolonging drugs such as Class IA (e.g. quinidine) and Class III (e.g. sotalol, dofetilide), antiarrhythmics, amiodarone, and antipsychotics (e.g. thioridazine, ziprasidone)
Treatment with potent or moderately potent CYP3A inhibitors including ketoconazole and other azole antifungals, diltiazem, verapamil, macrolide antibiotics, cyclosporine, or human immunodeficiency virus (HIV) protease inhibitors
The subject has previously received ranolazine within the 6-months prior to enrollment
The subject has received an investigational drug within 90 days prior to enrollment
Type 1 or type 2 diabetes mellitus
Congestive Heart Failure, ≥ New York Heart Association (NYHA) Class III
History of oxygen dependent Chronic Obstructive Pulmonary Disease (COPD)
Body Mass Index (BMI) >35