Clinical trial NCT02265796: Ranolazine Among Unrevascularized Chronic Stable Angina Patients
Official title: Improvement of Subjective Well-Being by Ranolazine Among Unrevascularized Chronic Stable Coronary Artery Disease Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
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
First posted: 2014-10-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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)

Primary outcomes:
measure: Seattle Angina Questionnaire Score Change From Baseline to 16 Weeks
timeFrame: Change in baseline to 16 weeks
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: NorthFlorida/South Georgia Veterans Health System, Gainesville, FL 32608
name: Anthony A Bavry, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.