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

Effect of Ranolazine After Deferral of Percutaneous Coronary Intervention by Fractional Flow Reserve (IMWELL3)

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.

Study Overview

• Status: Terminated
• 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 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 Type: Interventional
• Enrollment (Actual): 5
• 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 to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seattle Angina Questionnaire Score Change From 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).	Change in baseline to month 4

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	frequency of the number of 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; University of Florida
• Investigators: Principal Investigator: Anthony A Bavry, MD, MPH, North Florida/South Georgia Veterans Health System

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: May 22, 2014
• First Submitted That Met QC Criteria: May 27, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: fractional flow reserve; deferred percutaneous coronary intervention
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: 201400100