Microvascular Angina
Conditions
Keywords
Chest Pain, Microvascular Angina, Ranolazine, Emergency department, PET
Brief summary
The purpose of this study is to determine the effectiveness of Ranolazine for the treatment chest pain from disease of small vessels of the heart also known as 'microvascular angina'.
Detailed description
The Yale Chest Pain Center (CPC) is a unique clinical lab that provides an integrated interdisciplinary research team, access to high volume of chest pain patients largely free of coronary disease (93%) as well state of the art diagnostics including cardiac PET and a sophisticated system for serum processing and banking facilities. The CPC cohort represents a unique population with unrecognized microvascular disease and is often only accessible through the ED. We propose a one-year pilot study to understand the mechanisms of angina relief by Ranolazine (n=20) in patients with microvessel disease in the ED population as compared to controls (n=10) at baseline and at 1-month. In addition, changes in pain scores and function as measured by Seattle Angina Questionnaire (SAQ), recidivism and costs will be measured and correlated with changes in coronary flow reserve (CFR). Serum samples will be obtained and banked for future marker analysis as intermediate surrogates of outcomes. Primary aim: To compare changes in coronary flow reserve as measured by cardiac PET in patients receiving Ranolazine versus controls. Secondary aim: To determine if Ranolazine changes Seattle Angina Questionnaire (SAQ) scores in association with changes in Coronary Flow Reserve (CFR) versus controls. Exploratory aim: To compare composite rate of return visits (office, emergency department and hospitalization) for chest pain within 4-weeks of enrollment between patients with and without Ranolazine.
Interventions
DRUGRanolazine
Subjects will take the extended-release Ranolazine for a total of 4 weeks. Subjects will take 500 mg twice daily for the first week and then 1000 mg twice daily for remaining period (Dosing will be adjusted with concomitant use of diltiazem, verapamil, erythromycin, simvastatin or metformin).
DRUGPlacebo
Sponsors
Gilead Sciences
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients admitted to the Yale ED CPC * ≥ 30 years age * chest pain or angina equivalent as their chief complaint within 24 hours of enrollment * Coronary Flow Reserve(CFR) \<2.5 on PET scan in the ED.
Exclusion criteria
* Acute coronary syndrome * Prior evidence of obstructive heart disease (history of Percutaneous Transluminal Coronary Angioplasty (PTCA), Coronary Artery Bypass Grafting (CABG) or calcium score \> 10 on PET scan) * Resting blood pressure of systolic \>180/110 mm Hg or \<100/40 * known cardiomyopathy or heart failure * currently on dialysis * creatinine clearance \<30 ml/min * liver cirrhosis * significant aortic stenosis (murmur on exam) * active use of cocaine or amphetamine * current use of potent CYP3A4 inducers or inhibitors (such as ketoconazole, clarithromycin, HIV protease inhibitors) * baseline QTc \> 580 msec * use of drugs that prolong QTc (Haldol, erythromycin) * pregnancy * inability to read or understand English * suffering from a condition that precludes interview (i.e. cognitive or communication impairment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Flow Reserve | 4 weeks | Compare changes in coronary flow reserve as measured by cardiac PET(Positron Emission Tomography) in patients receiving Ranolazine versus control. This is the ratio between stress and rest myocardial blood flow in response to stress. |
Countries
United States
Participant flow
Recruitment details
This study was conducted from June, 2014-November, 2015 at the Yale New Haven Hospital Chest Pain Center, an ED observation unit that treats low-moderate cardiac risk patients.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group Subjects will take extended release Ranolazine for 4 weeks. Subjects will take 500 mg twice daily for the first week and then 1000 mg twice daily for remaining period (Dosing will be adjusted with concomitant use of diltiazem, verapamil, erythromycin, simvastatin or metformin). | 21 |
| Placebo Control Subjects will take placebo pill twice daily for 4 weeks. | 10 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo Control | Total | Intervention Group |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 5 | 50 years STANDARD_DEVIATION 9 | 50 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 23 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 22 Participants | 14 Participants |
| Sex: Female, Male Female | 9 Participants | 22 Participants | 13 Participants |
| Sex: Female, Male Male | 1 Participants | 9 Participants | 8 Participants |
| TIMI Score 0-1 | 9 Participants | 25 Participants | 16 Participants |
| TIMI Score 2-3 | 1 Participants | 6 Participants | 5 Participants |
| TIMI Score 4-7 | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 21 | 0 / 10 |
| serious Total, serious adverse events | 0 / 21 | 0 / 10 |
Outcome results
Primary
Coronary Flow Reserve
Compare changes in coronary flow reserve as measured by cardiac PET(Positron Emission Tomography) in patients receiving Ranolazine versus control. This is the ratio between stress and rest myocardial blood flow in response to stress.
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Coronary Flow Reserve | Baseline CFR | 1.6 ratio | Standard Deviation 0.3 |
| Intervention Group | Coronary Flow Reserve | Post-Treatment CFR | 1.9 ratio | Standard Deviation 0.4 |
| Placebo Control | Coronary Flow Reserve | Post-Treatment CFR | 1.6 ratio | Standard Deviation 0.4 |
| Placebo Control | Coronary Flow Reserve | Baseline CFR | 1.6 ratio | Standard Deviation 0.3 |
95% CI: [-0.08, 0.62]