RAMP-ED: Ranolazine and Microvascular Angina by PET in the Emergency Department
Study Details
Study Description
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'.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Ranolazine
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).
Other Names:
|
| Placebo Comparator: Placebo Control Subjects will take placebo pill twice daily for 4 weeks. |
Drug: Placebo
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale New Haven Hospital | New Haven | Connecticut | United States | 06510 |
Sponsors and Collaborators
- Yale University
- Gilead Sciences
Investigators
- Principal Investigator: Basmah Safdar, MD, Yale University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1312013144
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Intervention Group | Placebo Control |
|---|---|---|
| Arm/Group Description | 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). | Subjects will take placebo pill twice daily for 4 weeks. |
| Period Title: Overall Study | ||
| STARTED | 21 | 10 |
| COMPLETED | 17 | 8 |
| NOT COMPLETED | 4 | 2 |
Baseline Characteristics
| Arm/Group Title | Intervention Group | Placebo Control | Total |
|---|---|---|---|
| Arm/Group Description | 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). | Subjects will take placebo pill twice daily for 4 weeks. | Total of all reporting groups |
| Overall Participants | 21 | 10 | 31 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
50
(7)
|
50
(5)
|
50
(9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
13
61.9%
|
9
90%
|
22
71%
|
| Male |
8
38.1%
|
1
10%
|
9
29%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
3
14.3%
|
5
50%
|
8
25.8%
|
| Not Hispanic or Latino |
18
85.7%
|
5
50%
|
23
74.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
7
33.3%
|
2
20%
|
9
29%
|
| White |
14
66.7%
|
8
80%
|
22
71%
|
| More than one race |
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| TIMI Score (Count of Participants) | |||
| 0-1 |
16
76.2%
|
9
90%
|
25
80.6%
|
| 2-3 |
5
23.8%
|
1
10%
|
6
19.4%
|
| 4-7 |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Coronary Flow Reserve |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intervention Group | Placebo Control |
|---|---|---|
| Arm/Group Description | 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). | Subjects will take placebo pill twice daily for 4 weeks. |
| Measure Participants | 17 | 8 |
| Baseline CFR |
1.6
(0.3)
|
1.6
(0.3)
|
| Post-Treatment CFR |
1.9
(0.4)
|
1.6
(0.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intervention Group |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.27 | |
| Confidence Interval |
(2-Sided) 95% -0.08 to 0.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Intervention Group | Placebo Control | ||
| Arm/Group Description | 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). | Subjects will take placebo pill twice daily for 4 weeks. | ||
All Cause Mortality |
||||
| Intervention Group | Placebo Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Intervention Group | Placebo Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/21 (0%) | 0/10 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Intervention Group | Placebo Control | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/21 (14.3%) | 0/10 (0%) | ||
| General disorders | ||||
| Dizziness | 3/21 (14.3%) | 0/10 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Basmah Safdar |
|---|---|
| Organization | Yale School of Medicine |
| Phone | 2037853453 |
| basmah.safdar@yale.edu |
- 1312013144