Ranolazine Among Unrevascularized Chronic Stable Angina Patients (IMWELL)

Improvement of Subjective Well-Being by Ranolazine Among Unrevascularized Chronic Stable Coronary Artery Disease Patients

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 stable coronary artery disease patients who have demonstrable myocardial ischemia, but who do not undergo revascularization

Study Overview

• Status: Completed
• Conditions: Angina
• Intervention / Treatment: Drug: Ranolazine; Drug: Sugar pill

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 stable coronary artery disease patients who have demonstrable myocardial ischemia, but who do not undergo revascularization.

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.

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

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/South Georgia Veterans Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult 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
• QTc > 500 milliseconds
• 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 insufficiency (i.e. creatinine clearance < 30mL/min/1.73 m2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 500mg tablet two times per day for 7 days then,; 500mg tablet (1000mg) two times per day for 15 weeks; Other Names: placebo
Active Comparator: Ranolazine; Ranolazine 500 mg tablets; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks	The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life.Each of the 5 dimensions are scored by assigning eachresponse an ordinal value, beginning with 1 for the response that implies the lowest level of functioning, and summing across items within each of the 5 scales. Scale scores then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range1 / 3 Seattle Angina Questionnaire (SAQ)of the scale and multiplying by 100. No overall scale score is generated. Factors and Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life). .	Change in baseline to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Well Being	overall feeling of well being determined from rating of excellent, good, fair or poor at baseline compared to same at month 4	Compare from baseline to month 4
Ischemia Driven Revascularization or Hospitalization	Number of participants who reported adverse events for ischemia driven revascularization or hospitalization	4 month

Collaborators and Investigators

• Sponsor: North Florida Foundation for Research and Education
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Anthony A Bavry, MD, MPH, NorthFlorida/South Georgia Veterans Health System, Gainesville, FL 32608

Publications and helpful links

General Publications

• Bavry AA, Park KE, Choi CY, Mahmoud AN, Wen X, Elgendy IY. Improvement of Subjective Well-Being by Ranolazine in Patients with Chronic Angina and Known Myocardial Ischemia (IMWELL Study). Cardiol Ther. 2017 Jun;6(1):81-88. doi: 10.1007/s40119-016-0081-3. Epub 2017 Jan 2. Erratum In: Cardiol Ther. 2017 Jun;6(1):89.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: October 15, 2014
• First Posted (Estimate): October 16, 2014

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: fractional flow reserve; deferred percutaneous coronary intervention
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: 149-2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO