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

NCT00657514 | Withdrawn Phase 4 DMC

• 1 other identifier: 07-PAD-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Peripheral Arterial Disease; Angina

Keywords

hemoglobin desaturation kinetics; peripheral arterial disease; chronic angina; exercise tolerance

Outcome Measures

Primary Outcomes (1)

• skeletal muscle hemoglobin desaturation kinetics

  6 weeks

Secondary Outcomes (8)

• peak exercise oxygen consumption

  6 weeks

• Pulmonary oxygen uptake on-kinetics

  6 weeks

• Steady state level of tissue hemoglobin desaturation during exercise

  6 weeks

• Recovery kinetics of tissue oxygen saturation following exercise

  6 weeks

• adverse events

  6 weeks

Study Arms (2)

A

ACTIVE COMPARATOR

Drug arm - 500mg tablet po bid up to 1000mg (2 500mg tablets) po bid

Drug: Ranolazine

P

PLACEBO COMPARATOR

Placebo arm - 1 tablet po bid up to 2 tablets po bid if tolerated

Drug: Placebo

Interventions

Ranolazine DRUG

500mg tablet po bid up to 1000mg (2 500mg tablets) po bid

Also known as: Ranexa, extended-release tablets, CVT500, light orange, NDC Code: 67159-112-04

A

Placebo DRUG

1 tablet po bid up to 2 tablets po bid if tolerated

P

Eligibility Criteria

• Age: 40 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Colorado Prevention Center: lead

Study Sites (3)

University of Colorado at Denver

Aurora, Colorado, 80045, United States

Location

Denver Health and Hospital Authority (DHHA)

Denver, Colorado, 80204, United States

Location

Department of Veteran Affairs Medical Center

Denver, Colorado, 80220, United States

Location

Related Publications (3)

• Bauer TA, Regensteiner JG, Brass EP, Hiatt WR. Oxygen uptake kinetics during exercise are slowed in patients with peripheral arterial disease. J Appl Physiol (1985). 1999 Aug;87(2):809-16. doi: 10.1152/jappl.1999.87.2.809.

  PMID: 10444643 BACKGROUND

• Barstow TJ, Lamarra N, Whipp BJ. Modulation of muscle and pulmonary O2 uptakes by circulatory dynamics during exercise. J Appl Physiol (1985). 1990 Mar;68(3):979-89. doi: 10.1152/jappl.1990.68.3.979.

  PMID: 2341363 BACKGROUND

• Bauer TA, Brass EP, Hiatt WR. Impaired muscle oxygen use at onset of exercise in peripheral arterial disease. J Vasc Surg. 2004 Sep;40(3):488-93. doi: 10.1016/j.jvs.2004.06.025.

  PMID: 15337878 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease; Angina Pectoris

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Myocardial Ischemia; Heart Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mark R Nehler, MD

  The Univesity of Colorado at Denver

  PRINCIPAL INVESTIGATOR

• William R Hiatt, MD

  Colorado Prevention Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Section of Vascular Surgery and EndoVascular Therapy and Podiatry

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 15, 2014

Record last verified: 2014-08

Locations

US (3)