Clinical trial NCT02147834: Effectiveness of Ranolazine on Reducing Chest Pain in Patients With Blockage But no Stents
Official title: Effect of Ranolazine After Deferral of Percutaneous Coronary Intervention by Fractional Flow Reserve (IMWELL3)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Angina
Keywords: deferred percutaneous coronary intervention
fractional flow reserve
Lead sponsor: North Florida Foundation for Research and Education
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: University of Florida
First posted: 2014-05-28
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Seattle Angina Questionnaire Score Change From Baseline to Month 4
timeFrame: Change in baseline to month 4
Secondary outcomes:
measure: Subjective Well Being
timeFrame: Compare from baseline to month 4
measure: Ischemia Driven Revascularization or Hospitalization
timeFrame: 4 month
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System
state: Florida
Study officials:
affiliation: North Florida/South Georgia Veterans Health System
name: Anthony A Bavry, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: