EREDA: Effects of Ranolazine and Exercise on Daily Physical Activity Trial

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01948310
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 38
• Location: 1
• Arms: 2
• Duration (Months): 34.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The primary objective is to assess whether the increased angina threshold on ranolazine and subsequent higher training intensity will result in improved exercise tolerance and oxygen consumption; and greater than that observed with exercise training on placebo. The study team anticipates the chronic exercise improvements with ranolazine will be incrementally higher than the acute effects provided by ranolazine alone and demonstrated in previous trials. Key secondary objectives include the acute ranolazine and chronic exercise plus ranolazine effects on total daily energy expenditure (TDEE) and angina-related quality of life.

Condition or Disease	Intervention/Treatment	Phase
Chronic Stable Angina	Drug: Ranolazine; Behavioral: Aerobic Exercise; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Ranolazine and Exercise on Daily Physical Activity Trial
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Oct 10, 2016
• Actual Study Completion Date: Oct 10, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ranolazine plus Exercise Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.	Drug: Ranolazine; Comparison of Ranolazine 1000mg twice per day versus placebo twice per day; Other Names: Renexa ; Behavioral: Aerobic Exercise; Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test)
Placebo Comparator: Placebo plus Exercise Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.	Behavioral: Aerobic Exercise; Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test); Drug: Placebo; Comparison of placebo twice per day vs. Ranolazine 1000mg twice per day

Outcome Measures

Primary Outcome Measures

1. Change in Peak Oxygen Consumption (VO2 Max) [Baseline, Week 2 and Week 14]

   This test involves exercising on a treadmill or bike to maximal exertion, during which the subject's breathing and oxygen consumption are measured. Under a set study protocol, treadmill or bike workload will increase every minute until the participant either chooses to end the test or the study personnel choose to end the test for safety purposes.

Secondary Outcome Measures

1. Change in Treatment Satisfaction as Measured by the Seattle Angina Questionnaire [Baseline, Week 2 and Week 14]

   The Treatment Satisfaction scale is one of five scales of the Seattle Angina Questionnaire. The possible range of scores is 0 to 100, with higher scores indicating better quality of life.

2. Change in Total Daily Energy Expenditure [Week 1, Week 4 and Week 14]

   Total daily physical activity is measured via Actigraph GT3X accelerometers. Accelerometers will be worn for 7 days pre-drug, post-drug/pre-exercise (week 4) and again in the final month of the exercise intervention (week 13)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented CAD diagnosis

• Stable angina ≥ 3 months

Exclusion Criteria:

• Class III or IV heart failure

• Myocardial Infarction or coronary revascularization procedure within 2 months

• QT interval > 500ms or prescribed medication known to prolong the QTc interval

• Contraindicated Medications

• Metformin dose > 1700mg/day

• Class Ia, Ic and III anti-arrhythmics

• CYP3A inhibitors

• Simvastatin >20mg/day

• Severe renal disease (< 30ml/min creatinine clearance)

• Currently on dialysis

• Lack of transportation to the exercise and testing facilities

• Implanted pacemaker that is not rate responsive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Center for Living	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• Gilead Sciences

Investigators

• Principal Investigator: William E Kraus, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01948310
• Other Study ID Numbers: Pro00045794
• First Posted: Sep 23, 2013
• Last Update Posted: Dec 12, 2017
• Last Verified: Nov 1, 2017

• Additional relevant MeSH terms: Angina, Stable; Ranolazine

Study Results

Participant Flow

Recruitment Details	Thirty-eight subjects were recruited for this study. One dropped out before randomization.

Arm/Group Title	Placebo Plus Exercise	Ranolazine Plus Exercise
Arm/Group Description	Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. Aerobic Exercise: Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test) Placebo: Comparison of placebo twice per day vs. Ranolazine 1000mg twice per day	Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. Ranolazine: Comparison of Ranolazine 1000mg twice per day versus placebo twice per day Aerobic Exercise: Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test)
Period Title: Overall Study
STARTED	19	18
COMPLETED	16	13
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Placebo Plus Exercise	Ranolazine Plus Exercise	Total
Arm/Group Description	Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. Aerobic Exercise: Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test) Placebo: Comparison of placebo twice per day vs. Ranolazine 1000mg twice per day	Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. Ranolazine: Comparison of Ranolazine 1000mg twice per day versus placebo twice per day Aerobic Exercise: Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test)	Total of all reporting groups
Overall Participants	19	18	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (8.3)	67.4 (11.2)	68.4 (9.6)
Sex: Female, Male (Count of Participants)
Female	6 31.6%	7 38.9%	13 35.1%
Male	13 68.4%	11 61.1%	24 64.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 31.6%	5 27.8%	11 29.7%
White	13 68.4%	13 72.2%	26 70.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	19 100%	18 100%	37 100%

Outcome Measures

1. Primary Outcome

Title	Change in Peak Oxygen Consumption (VO2 Max)
Description	This test involves exercising on a treadmill or bike to maximal exertion, during which the subject's breathing and oxygen consumption are measured. Under a set study protocol, treadmill or bike workload will increase every minute until the participant either chooses to end the test or the study personnel choose to end the test for safety purposes.
Time Frame	Baseline, Week 2 and Week 14

Outcome Measure Data

Analysis Population Description

Subjects who completed the study were included in the analysis

Arm/Group Title	Placebo Plus Exercise	Ranolazine Plus Exercise
Arm/Group Description	Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.	Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.
Measure Participants	16	13
Change at 2 weeks	0.03 (1.2)	0.38 (1.9)
Change at 14 weeks	0.9 (1.5)	2.1 (3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus Exercise
	Comments	2-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus Exercise
	Comments	0-14 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ranolazine Plus Exercise
	Comments	2-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ranolazine Plus Exercise
	Comments	14-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Treatment Satisfaction as Measured by the Seattle Angina Questionnaire
Description	The Treatment Satisfaction scale is one of five scales of the Seattle Angina Questionnaire. The possible range of scores is 0 to 100, with higher scores indicating better quality of life.
Time Frame	Baseline, Week 2 and Week 14

Outcome Measure Data

Analysis Population Description

Subjects who completed the study were included in the analysis

Arm/Group Title	Placebo Plus Exercise	Ranolazine Plus Exercise
Arm/Group Description	Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.	Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.
Measure Participants	16	13
2-0 Weeks	0.8 (9.1)	5.3 (8.0)
14-0 weeks	3.1 (13.3)	-1.0 (13.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus Exercise
	Comments	2-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus Exercise
	Comments	14-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ranolazine Plus Exercise
	Comments	2-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ranolazine Plus Exercise
	Comments	14-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change in Total Daily Energy Expenditure
Description	Total daily physical activity is measured via Actigraph GT3X accelerometers. Accelerometers will be worn for 7 days pre-drug, post-drug/pre-exercise (week 4) and again in the final month of the exercise intervention (week 13)
Time Frame	Week 1, Week 4 and Week 14

Outcome Measure Data

Analysis Population Description

Subjects who completed the study were included in the analysis.

Arm/Group Title	Placebo Plus Exercise	Ranolazine Plus Exercise
Arm/Group Description	Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.	Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold.
Measure Participants	16	13
2-0 weeks	2.0 (39.3)	-7.6 (29.3)
14-0 weeks	22.2 (54.2)	24.3 (29.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus Exercise
	Comments	2-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Plus Exercise
	Comments	0-14 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ranolazine Plus Exercise
	Comments	2-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ranolazine Plus Exercise
	Comments	14-0 weeks
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse events were collected from baseline until Week 14.
Arm/Group Title	Ranolazine Plus Exercise		Placebo Plus Exercise
Arm/Group Description	Ranolazine 1000mg pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. Ranolazine: Comparison of Ranolazine 1000mg twice per day versus placebo twice per day Aerobic Exercise: Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test)		Placebo pill twice per day plus aerobic exercise three times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold. Aerobic Exercise: Aerobic exercise 3 times per week, 45 minutes per session at an intensity of 10-20 beats per minute below the angina threshold (heart rate at which angina symptoms began on the stress test) Placebo: Comparison of placebo twice per day vs. Ranolazine 1000mg twice per day
All Cause Mortality
	Ranolazine Plus Exercise		Placebo Plus Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/19 (0%)
Serious Adverse Events
	Ranolazine Plus Exercise		Placebo Plus Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Ranolazine Plus Exercise		Placebo Plus Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		1/19 (5.3%)
Cardiac disorders
mild myocardial infarction	0/18 (0%)	0	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.