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

This study has been withdrawn prior to enrollment.
(Insufficient enrollment)
Sponsor:
Information provided by (Responsible Party):
Mark Nehler, MD, Colorado Prevention Center
ClinicalTrials.gov Identifier:
NCT00657514
First received: April 8, 2008
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Peripheral Arterial Disease
Angina
Drug: Ranolazine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Ranolazine on Skeletal Muscle Endpoints During Exercise In Subjects With Chronic Angina and Peripheral Arterial Disease

Resource links provided by NLM:


Further study details as provided by Colorado Prevention Center:

Primary Outcome Measures:
  • skeletal muscle hemoglobin desaturation kinetics [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • peak exercise oxygen consumption [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Pulmonary oxygen uptake on-kinetics [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Steady state level of tissue hemoglobin desaturation during exercise [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Recovery kinetics of tissue oxygen saturation following exercise [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • adverse events [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Peak Walking Time (PWT) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Claudication Onset Time (COT) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Time to Onset of Angina (TOA) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: May 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Drug arm - 500mg tablet po bid up to 1000mg (2 500mg tablets) po bid
Drug: Ranolazine
500mg tablet po bid up to 1000mg (2 500mg tablets) po bid
Other Names:
  • Ranexa, extended-release tablets
  • CVT500
  • light orange
  • NDC Code: 67159-112-04
Placebo Comparator: P
Placebo arm - 1 tablet po bid up to 2 tablets po bid if tolerated
Drug: Placebo
1 tablet po bid up to 2 tablets po bid if tolerated

  Hide Detailed Description

Detailed 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:

  1. Males age > 40 years.
  2. 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.

  3. 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
  4. 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:

  1. Non-atherosclerotic diseases of the peripheral circulation by clinical history
  2. Unable to complete the first stage of the modified, extended Astrand treadmill protocol
  3. Clinically significant ECG abnormalities or changes with exercise on the screening ECG
  4. Evidence of critical limb ischemia (CLI)
  5. Hepatic impairment (Child-Pugh Classes A [mild], B [moderate], or C [severe])
  6. End stage renal disease requiring dialysis
  7. Hemoglobin < 12 mg/dL.
  8. Platelet count < 90,000/mL.
  9. Planned surgical/endovascular intervention for coronary artery disease (CAD) or peripheral arterial disease (PAD) in the next 3 months
  10. Maximal exercise is limited by symptoms other than claudication or angina
  11. 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
  12. Known allergy to ranolazine
  13. 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
  14. 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)
  15. 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
  16. The subject has previously received ranolazine within the 6-months prior to enrollment
  17. The subject has received an investigational drug within 90 days prior to enrollment
  18. Type 1 or type 2 diabetes mellitus
  19. Congestive Heart Failure, ≥ New York Heart Association (NYHA) Class III
  20. History of oxygen dependent Chronic Obstructive Pulmonary Disease (COPD)
  21. Body Mass Index (BMI) >35
  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00657514

Locations
United States, Colorado
University of Colorado at Denver
Aurora, Colorado, United States, 80045
Denver Health and Hospital Authority (DHHA)
Denver, Colorado, United States, 80204
Department of Veteran Affairs Medical Center
Denver, Colorado, United States, 80220
Sponsors and Collaborators
Colorado Prevention Center
Investigators
Principal Investigator: Mark R Nehler, MD The Univesity of Colorado at Denver
Study Chair: William R Hiatt, MD Colorado Prevention Center
  More Information

Publications:
Responsible Party: Mark Nehler, MD, Chief, Section of Vascular Surgery and EndoVascular Therapy and Podiatry, Colorado Prevention Center
ClinicalTrials.gov Identifier: NCT00657514     History of Changes
Other Study ID Numbers: 07-PAD-01
Study First Received: April 8, 2008
Last Updated: August 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Colorado Prevention Center:
hemoglobin desaturation kinetics
peripheral arterial disease
chronic angina
exercise tolerance

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Vascular Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014