IMWELL3: Effectiveness of Ranolazine on Reducing Chest Pain in Patients With Blockage But no Stents

• Sponsor: North Florida Foundation for Research and Education (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02147834
• Collaborator: Gilead Sciences (Industry), University of Florida (Other)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 13
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To determine if ranolazine improves angina symptoms at 4 months compared with placebo among patients who are deferred for receiving a Percutaneous Coronary Intervention (PCI) based on the Fractional Flow Reserve (FFR) measurement.

Condition or Disease	Intervention/Treatment	Phase
Angina	Drug: Ranolazine; Drug: Sugar pill	Phase 2

Detailed Description

This is a prospective, double-blind, placebo-controlled, randomized, single-center (North Florida- South Georgia VA Medical Center) study. The study objective is to determine if ranolazine improves angina symptoms at 4 months compared with placebo among patients who are deferred from having a PCI based on the FFR measurement.

Baseline Procedure:

Assessments performed exclusively to determine eligibility for this study would be done only after obtaining informed consent. Assessments performed for clinical indications (not exclusively to determine study eligibility) may be used for baseline values even if the studies were done before informed consent was obtained. The assessment will include:

• Informed Consent

• Review subject eligibility criteria

• FFR value calculated at the time of cardiac catheterization

• Review previous and concomitant medications

• Frequency of symptoms and quality of life prior to study according to Seattle Angina Questionnaire (SAQ)

Screening Visit:

The assessments to determine eligibility are:

• Review of eligibility criteria

• Review of cardiac catheterization and FFR

• Review of medications taken in the past 30 days

Subjects that meet eligibility criteria will be randomized to receive either the active drug, Ranolazine or a matching placebo (non-active drug). Staff and subjects will not know if the subject will be receiving the active drug or the placebo.

Drug schedule will be as follows:

• 1st dose of one tablet (500mg) will begin the evening of Day 1

• On Days 2-7, one tablet (500mg) two times a day (12-hours apart).

• On Day 8, increase dose of study drug to two tablets (1000mg) twice a day; once in the morning and once in the evening, 12 hours apart. This dose will continue for the duration of the study. The study drug can be taken with or without food.

Telephone Follow-up:

One week phone calls will be made to determine well being, adverse events, answer questions and remind subjects to increase the study medication dose.

Two month phone calls will be made to determine well being and adverse events.

Month 4 Follow-up:

• Frequency of symptoms and quality of life according to Seattle Angina Questionnaire (SAQ)

• Assessment of well-being

• Any hospitalizations or the need for revascularization

Subjects will take the study medication for 16 weeks and will receive a phone call from the study coordinator 30 days after last dose of study medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Ranolazine After Deferral of Percutaneous Coronary Intervention by Fractional Flow Reserve (IMWELL3)
• Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ranolazine Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Drug: Ranolazine; Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks; Other Names: Ranexa
Placebo Comparator: Sugar pill Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Drug: Sugar pill; sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Seattle Angina Questionnaire Score Change From Baseline to Month 4 [Change in baseline to month 4]

   The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease (physical limitation, anginal stability, anginal frequency, treatment satisfaction, and disease perception).

Secondary Outcome Measures

1. Subjective Well Being [Compare from baseline to month 4]

   overall feeling of well being determined from rating of excellent, good, fair or poor at baseline compared to same at month 4

2. Ischemia Driven Revascularization or Hospitalization [4 month]

   frequency of the number of reported adverse events for ischemia driven revascularization or hospitalization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stable patients >= 18 years of age referred for cardiac catheterization for evaluation of cardiac symptoms ( angina, fatigue, or shortness of breath)

• At least 1 indeterminate stenosis (20-80%), fractional flow reserve (FFR) >=0.8 and PCI deferred

Exclusion Criteria:

• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) during the index procedure or anticipated within the next month

• acute coronary syndrome or cardiogenic shock

• use of strong inhibitors of CTP3A (i.e. ketoconazole, itraconazole, clarithromycin,nefazodone, nelfinavir, ritonavir, indinavir and saquinavir)

• use of inducers of CYP3A (i.e. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort)

• liver cirrhosis

• sever renal insufficience (i.e. creatinine clearance < 30mL/min/1.73 m2)

• QTc > 500 milliseconds

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Florida/South Georgia Veterans Health System	Gainesville	Florida	United States	32608

Sponsors and Collaborators

• North Florida Foundation for Research and Education
• Gilead Sciences
• University of Florida

Investigators

• Principal Investigator: Anthony A Bavry, MD, MPH, North Florida/South Georgia Veterans Health System

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: North Florida Foundation for Research and Education
• ClinicalTrials.gov Identifier: NCT02147834
• Other Study ID Numbers: 201400100
• First Posted: May 28, 2014
• Last Update Posted: Jun 11, 2019
• Last Verified: May 1, 2019

• Keywords provided by North Florida Foundation for Research and Education: deferred percutaneous coronary intervention; fractional flow reserve
• Additional relevant MeSH terms: Ranolazine

Study Results

Participant Flow

Recruitment Details	5 subjects enrolled. First subjected enrolled 8/7/2015 and last enrolled on 11/19/2015. enrollment discontinued early by investigator due to futility.

Arm/Group Title	Ranolazine	Sugar Pill
Arm/Group Description	Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Ranolazine: Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks
Period Title: Overall Study
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ranolazine	Sugar Pill	Total
Arm/Group Description	Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Ranolazine: Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 33.3%	0 0%	1 20%
>=65 years	2 66.7%	2 100%	4 80%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	3 100%	2 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Seattle Angina Questionnaire Score Change From Baseline to Month 4
Description	The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease (physical limitation, anginal stability, anginal frequency, treatment satisfaction, and disease perception).
Time Frame	Change in baseline to month 4

Outcome Measure Data

Analysis Population Description

The investigator ended this project early due to futility. Do data was analyzed.

Arm/Group Title	Ranolazine	Sugar Pill
Arm/Group Description	Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Ranolazine: Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks
Measure Participants	0	0

2. Secondary Outcome

Title	Subjective Well Being
Description	overall feeling of well being determined from rating of excellent, good, fair or poor at baseline compared to same at month 4
Time Frame	Compare from baseline to month 4

Outcome Measure Data

Analysis Population Description

The investigator ended this study early due to futility. no data was analyzed.

Arm/Group Title	Ranolazine	Sugar Pill
Arm/Group Description	Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Ranolazine: Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks
Measure Participants	0	0

3. Secondary Outcome

Title	Ischemia Driven Revascularization or Hospitalization
Description	frequency of the number of reported adverse events for ischemia driven revascularization or hospitalization
Time Frame	4 month

Outcome Measure Data

Analysis Population Description

The investigator ended this study early due to futility. No data was analyzed.

Arm/Group Title	Ranolazine	Sugar Pill
Arm/Group Description	Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Ranolazine: Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks	Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks
Measure Participants	0	0

Adverse Events

Time Frame	baseline to 4 months.
Arm/Group Title	Ranolazine		Sugar Pill
Arm/Group Description	Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Ranolazine: Ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks		Sugar pill that looks like the drug ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks Sugar pill: sugar pill manufactured to mimic ranolazine 500mg tablet 500mg tablet two times per day for 7 days then, 500mg tablet (1000mg) two times per day for 15 weeks
All Cause Mortality
	Ranolazine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranolazine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Ranolazine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

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.