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

• Sponsor: William Beaumont Hospitals (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00914316
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arms: 4
• Duration (Months): 46
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease	Drug: Ranolazine; Drug: Placebo	N/A

Detailed Description

The treatment groups are:

1. Group A will be randomized to a 12 week supervised exercise program and ranolazine, (Ranexa) 1000 mg orally, twice daily, by mouth.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Supervised Treadmill Exercise and Ranolazine for Intermittent Claudication of Lower Extremities. THE STERILE TRIAL.
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Phase 1-Ranolazine, Phase 2-Ranolazine 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; Ranolazine, 1000 mg, capsule, twice daily, by mouth.; Other Names: Ranexa
Active Comparator: Phase 1 -Ranolazine, Phase 2 -Placebo 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; Ranolazine, 1000 mg, capsule, twice daily, by mouth.; Other Names: Ranexa ; Drug: Placebo; twice daily; Other Names: sugar pill
Active Comparator: Phase 1 -Placebo, Phase 2 -Ranolazine 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; Ranolazine, 1000 mg, capsule, twice daily, by mouth.; Other Names: Ranexa ; Drug: Placebo; twice daily; Other Names: sugar pill
Placebo Comparator: Phase 1 -Placebo, Phase 2 -Placebo 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; twice daily; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Percentage Increase in Absolute Walking Distance Following Phase 1 [12 weeks]

   Change in absolute walking distance in meters from baseline to 12 week follow-up treadmill test, as a percentage from baseline treadmill test

Secondary Outcome Measures

1. Percentage Increase in Absolute Walking Distance Following Phase 2 [24 weeks]

   Change in absolute walking distance in meters from baseline to 24 week follow-up treadmill test, as a percentage from baseline treadmill test

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	William Beaumont Hospital	Royal Oak	Michigan	United States	48073

Sponsors and Collaborators

• William Beaumont Hospitals

Investigators

• Principal Investigator: Laura Franny, M.D., William Beaumont Hospitals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William Beaumont Hospitals
• ClinicalTrials.gov Identifier: NCT00914316
• Other Study ID Numbers: 2009-051
• First Posted: Jun 4, 2009
• Last Update Posted: Aug 9, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by William Beaumont Hospitals: Lower leg claudication; Poor circulation of the leg muscles; Cramping or discomfort in the lower legs; Lower leg pain; PAD (Peripheral arterial disease)
• Additional relevant MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication; Ranolazine

Study Results

Participant Flow

Arm/Group Title	Phase 1-Ranolazine, Phase 2-Ranolazine	Phase 1 -Ranolazine, Phase 2 -Placebo	Phase 1 -Placebo, Phase 2 -Ranolazine	Phase 1 -Placebo, Phase 2 -Placebo
Arm/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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth.	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Placebo: twice daily
Period Title: Phase 1
STARTED	7	6	8	8
COMPLETED	2	4	3	6
NOT COMPLETED	5	2	5	2
Period Title: Phase 1
STARTED	2	4	3	6
COMPLETED	1	4	2	6
NOT COMPLETED	1	0	1	0

Baseline Characteristics

Arm/Group Title	Phase 1-Ranolazine, Phase 2-Ranolazine	Phase 1 -Ranolazine, Phase 2 -Placebo	Phase 1 -Placebo, Phase 2 -Ranolazine	Phase 1 -Placebo, Phase 2 -Placebo	Total
Arm/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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth.	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Placebo: twice daily	Total of all reporting groups
Overall Participants	3	6	6	8	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 33.3%	2 33.3%	1 16.7%	4 50%	8 34.8%
>=65 years	2 66.7%	4 66.7%	5 83.3%	4 50%	15 65.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.0 (3.6)	69.7 (6.9)	77.0 (10.5)	65.8 (14.9)	70.1 (11.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 33.3%	1 16.7%	0 0%	3 13%
Male	3 100%	4 66.7%	5 83.3%	8 100%	20 87%
Region of Enrollment (Count of Participants)
United States	3 100%	6 100%	6 100%	8 100%	23 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Missing data for 12 week test in 1 subject in Ranolazine/Ranolazine group, 1 subject in Ranolazine/placebo group, and 3 subjects in placebo/placebo group

Arm/Group Title	Phase 1-Ranolazine, Phase 2-Ranolazine	Phase 1 -Ranolazine, Phase 2 -Placebo	Phase 1 -Placebo, Phase 2 -Ranolazine	Phase 1 -Placebo, Phase 2 -Placebo
Arm/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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth.	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Placebo: twice daily
Measure Participants	1	3	3	3
Median (Inter-Quartile Range) [percentage of baseline]	112	108	145	155

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Missing data from one subject 24 week treadmill test in placebo/placebo group

Arm/Group Title	Phase 1-Ranolazine, Phase 2-Ranolazine	Phase 1 -Ranolazine, Phase 2 -Placebo	Phase 1 -Placebo, Phase 2 -Ranolazine	Phase 1 -Placebo, Phase 2 -Placebo
Arm/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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth.	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily	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. Placebo: twice daily
Measure Participants	1	4	2	5
Median (Inter-Quartile Range) [percentage of baeline]	98	120	181	145

Adverse Events

Time Frame	28 weeks
Adverse Event Reporting Description	Only 8 adverse events were collected: death, unstable angina, ischemic ST depression > 2 mm during exercise training, myocardial infarction, cerebrovascular accident, ventricular arrhythmias (non-sustained ventricular tachycardia (VT), sustained VT, ventricular fibrillation), advanced heart block (Mobitz II or Type III heart block), and congestive heart failure (CHF) requiring hospitalization. Adverse events were collected for the 20 patients completing at least baseline testing in Phase 1.
Arm/Group Title	Phase 1-Ranolazine, Phase 2-Ranolazine		Phase 1 -Ranolazine, Phase 2 -Placebo		Phase 1 -Placebo, Phase 2 -Ranolazine		Phase 1 -Placebo, Phase 2 -Placebo
Arm/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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth.		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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily		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. Ranolazine: Ranolazine, 1000 mg, capsule, twice daily, by mouth. Placebo: twice daily		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. Placebo: twice daily
All Cause Mortality
	Phase 1-Ranolazine, Phase 2-Ranolazine		Phase 1 -Ranolazine, Phase 2 -Placebo		Phase 1 -Placebo, Phase 2 -Ranolazine		Phase 1 -Placebo, Phase 2 -Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/5 (0%)		0/4 (0%)		0/8 (0%)
Serious Adverse Events
	Phase 1-Ranolazine, Phase 2-Ranolazine		Phase 1 -Ranolazine, Phase 2 -Placebo		Phase 1 -Placebo, Phase 2 -Ranolazine		Phase 1 -Placebo, Phase 2 -Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/5 (0%)		0/4 (0%)		0/8 (0%)
Cardiac disorders
myocardial infarction	1/3 (33.3%)	1	0/5 (0%)	0	0/4 (0%)	0	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Phase 1-Ranolazine, Phase 2-Ranolazine		Phase 1 -Ranolazine, Phase 2 -Placebo		Phase 1 -Placebo, Phase 2 -Ranolazine		Phase 1 -Placebo, Phase 2 -Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/5 (0%)		0/4 (0%)		0/8 (0%)

Limitations/Caveats

Early termination due to recruitment and retention difficulties, leading to small numbers of subjects. Missing data for several subjects.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.