Microvascular Coronary Dysfunction (MCD)RWISENCT01342029
Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia
A study testing Ranolazine in people with Microvascular Coronary Dysfunction (MCD), run by Cedars-Sinai Medical Center at 2 sites in United States.
Trial summary
This research study is designed to test the use of ranolazine in patients with angina (chest discomfort due to reduced blood supply to the heart) due to microvascular coronary dysfunction (MCD; abnormalities in the small blood vessels of the heart). This drug is approved by the U.S. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Microvascular Coronary Dysfunction (MCD)
- What is being tested?
- Ranolazine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 142 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2011to Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women age >18 from diverse racial/ethnic groups;
- Competent to give informed consent;
- Patients with chronic angina or its equivalent;
- Coronary angiogram revealing MCD with no obstructive CAD (epicardial coronary stenosis <50% luminal diameter stenosis);
- Left ventricular ejection fraction > or = 45%;
- Objective evidence of ischemia by noninvasive methods such as exercise stress test, stress Echo, MRI, or SPECT;
- Patients with 10% myocardial ischemia by Cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index ≤ 2.0 or abnormal coronary reactivity testing (CFR < 2.5, or ACH response of no dilation or constriction, determined by local site read).
Who cannot join
- Acute coronary syndrome (defined by WHO), cardiogenic shock or requiring inotropic or intra-aortic balloon support;
- Planned percutaneous coronary intervention or CABG or established obstructive CAD with ischemia eligible for revascularization, acute MI;
- Prior non-cardiac illness with an estimated life expectancy <4 years;
- Unable to give informed consent;
- Allergy or contra-indication to CMRI testing, including renal failure, claustrophobia, and asthma, uncontrolled moderate hypertension (sitting blood pressure >160/95mmHg with measurements recorded on at least 2 occasions), conditions likely to influence outcomes: Severe lung, creatinine >1.8 or CrCl ≤ 50ml/min) or hepatic disease;
- Surgically uncorrected significant congenital or valvular heart disease and other disease likely to be fatal or require frequent hospitalization within the next six months;
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- Adherence or retention reasons;
- Unwilling to complete follow-up evaluation including repeat testing, documented obstructive hypertrophic cardiomyopathy;
- Aortic stenosis (valve area <1.5cm);
- LV dysfunction (ejection fraction ≤35%);
- History of significant cocaine or amphetamine abuse;
- Taking potent CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir);
- Women who are pregnant.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32610
127 S. San Vicente Blvd, Suite A9303
Los Angeles, California, 90048
About this study
This research study is designed to test the use of ranolazine in patients with angina (chest discomfort due to reduced blood supply to the heart) due to microvascular coronary dysfunction (MCD; abnormalities in the small blood vessels of the heart). This drug is approved by the U.S. Food and Drug Administration (FDA) for treatment of chronic angina. The FDA has approved this drug based on studies primarily on patients with chronic angina with major blockages of the arteries.
Read the detailed description
This is a randomized, double-blinded, placebo- controlled, and cross-over clinical trial. 147 subjects will be enrolled at two clinical sites, with projected 9-10% dropout and anticipated 134 completed subjects. To maintain blinding of the investigators, the study randomization table will be kept in Pharmacy Service. The sponsor will ship the study drug directly to the Pharmacy Service. The pharmacy service will also be responsible for dispersing the study drug.
There are 4 study visits (2 visits in each study period) in this study. Subjects will be in this study for about 6 weeks from Week 0 - baseline visit to Week 6 - exit visit. Besides the procedure of study medication mentioned above, other study procedures include informed consent, physical exam, questionnaires, EKG for safety assessment, blood collection for laboratory testing, cardiac MRI, and follow-up events. In sum, participants will be asked to undergo 2 cardiac MRI's and fill out questionnaires 4 times. They will be asked to participate for 6 weeks with two 2-week courses (with a treatment window period of 5 days), one with ranolazine and the other with placebo (without knowing which they are taking). There is a 2-week washout period between treatments. The participants will otherwise remain on all their usual medications. The physicians will also be blinded to which medication the subject is receiving.
Participation in this study will be approximately 6 weeks, which consists of two 2-week study periods and in between a 2-week washout period:
- During the first 2-week period: Subjects will be randomized to first receive either the ranolazine or a placebo pill (sugar pill with no active medicine). Subjects will take the extended-release ranolazine or a placebo pill for a total of 2 weeks. Subjects will take 500 mg twice daily for the first 1 week and then 1000 mg twice daily for an additional 1 week. Subjects who are unable to take the higher dose due to side effects will remain on 500 mg twice daily for the entire study period. After the 2 weeks, the participant will have a Cardiac MRI and complete study questionnaires. These tools will allow us to evaluate if the participant is doing better on the medication.
- 2-week washout period: Subject will then be asked to go 2 weeks without any study medication (ranolazine or placebo).
- During the second 2-week period: Subject will then be given either extended release ranolazine or placebo depending on which was received the first time for a total of 2 weeks. Subjects will take 500 mg twice daily for the first 1 week and then 1000 mg twice daily for an additional 1 week. Subjects who are unable to take the higher dose due to side effects will remain on 500 mg twice daily for entire study period. This 2-week period will again be followed by a final Cardiac MRI and questionnaire completion.
- Conditions
- Microvascular Coronary Dysfunction (MCD)
- Being tested
- Ranolazine, Placebo
- Keywords
- Microvascular Coronary Dysfunction (MCD)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Ranexa
This drug is approved by the U.S. Food and Drug Administration (FDA) for treatment of chronic angina.
500-1,000 mg po bid for 2 weeks
PlaceboDrug
500-1,000 mg po bid for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ranolazine | Experimental | 147 subjects, with projected 9-10% dropout and anticipated 134 completed subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 500-1,000 mg po bid for 2 weeks with exit testing followed by cross-over to the alternate ranolazine or placebo and repeat exit testing. Receives: Drug: Ranolazine |
| Placebo | Placebo comparator | 147 subjects, with projected 9-10% dropout and anticipated 134 completed subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 500-1,000 mg po bid for 2 weeks with exit testing followed by cross-over to the alternate ranolazine or placebo and repeat exit testing. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seattle Angina Questionnaire (SAQ)
Questionnaires will be completed (SAQ - Seattle Angina Questionnaire) at the end of each treatment period.
The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important.
Measured: 2 weeks (first intervention) and 6 weeks (second intervention)
Secondary outcomes (1)
Cardiac Magnetic Resonance (CMRs)
Cardiac Magnetic Resonance (CMRs) (CMR 1 and CMR 2) end of the 2nd week of treatment 1 and treatment 2 respectively, 4 hours after the morning dose of study drug was performed to measure myocardial perfusion reserve index.
Myocardial perfusion reserve index (MPRI) was assessed using the first-pass perfusion intensity curves during stress and rest cardiac magnetic resonance imaging. First-pass perfusion images were analysed using CAAS MRV CMRI analysis software Version 3.3 (Pie Medical Imaging B.V., Maastricht, the Netherlands). Global MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope.
Higher MPRI represents better myocardial perfusion reserve. Since MPRI is an index, there is no unit.
Measured: 2 weeks (first intervention) and 6 weeks (second intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Microvascular Coronary Dysfunction (MCD)Studies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florida
- Responsible party
- Principal investigator, Noel Bairey Merz, Cedars-Sinai Medical Center
- Investigators
- C. Noel Bairey Merz, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01342029
- Sponsor's protocol ID
- IN-US-259-0124 - RWISE
- Acronym
- RWISE
- Status last verified
- Apr 2019
- First submitted
- 22 Apr 2011
- Last updated
- 24 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Rambarat CA, Elgendy IY, Handberg EM, Bairey Merz CN, Wei J, Minissian MB, Nelson MD, Thomson LEJ, Berman DS, Shaw LJ, Cook-Wiens G, Pepine CJ. Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study. Int J Cardiol. 2019 Feb 1;276:8-13. doi: 10.1016/j.ijcard.2018.09.081. Epub 2018 Sep 26.
PubMed 30293664Birkeland K, Khandwalla RM, Kedan I, Shufelt CL, Mehta PK, Minissian MB, Wei J, Handberg EM, Thomson LE, Berman DS, Petersen JW, Anderson RD, Cook-Wiens G, Pepine CJ, Bairey Merz CN. Daily Activity Measured With Wearable Technology as a Novel Measurement of Treatment Effect in Patients With Coronary Microvascular Dysfunction: Substudy of a Randomized Controlled Crossover Trial. JMIR Res Protoc. 2017 Dec 20;6(12):e255. doi: 10.2196/resprot.8057.
PubMed 29263019Bairey Merz CN, Handberg EM, Shufelt CL, Mehta PK, Minissian MB, Wei J, Thomson LE, Berman DS, Shaw LJ, Petersen JW, Brown GH, Anderson RD, Shuster JJ, Cook-Wiens G, Rogatko A, Pepine CJ. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J. 2016 May 14;37(19):1504-13. doi: 10.1093/eurheartj/ehv647. Epub 2015 Nov 27.
PubMed 26614823
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia
- ClinicalTrials.gov ID
- NCT01342029
- Acronym / sponsor ID
- RWISE / IN-US-259-0124 - RWISE
- Conditions
- Microvascular Coronary Dysfunction (MCD)
- Keywords
- Microvascular Coronary Dysfunction (MCD)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- University of Florida
- Study start
- May 2011 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 26 Apr 2011 (estimated)
- Results
- Posted 12 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is designed to test the use of ranolazine in patients with angina (chest discomfort due to reduced blood supply to the heart) due to microvascular coronary dysfunction (MCD; abnormalities in the small blood vessels of the heart). This drug is approved by the U.S. Food and Drug Administration (FDA) for treatment of chronic angina. The FDA has approved this drug based on studies primarily on patients with chronic angina with major blockages of the arteries.
Detailed description
This is a randomized, double-blinded, placebo- controlled, and cross-over clinical trial. 147 subjects will be enrolled at two clinical sites, with projected 9-10% dropout and anticipated 134 completed subjects. To maintain blinding of the investigators, the study randomization table will be kept in Pharmacy Service. The sponsor will ship the study drug directly to the Pharmacy Service. The pharmacy service will also be responsible for dispersing the study drug.
There are 4 study visits (2 visits in each study period) in this study. Subjects will be in this study for about 6 weeks from Week 0 - baseline visit to Week 6 - exit visit. Besides the procedure of study medication mentioned above, other study procedures include informed consent, physical exam, questionnaires, EKG for safety assessment, blood collection for laboratory testing, cardiac MRI, and follow-up events. In sum, participants will be asked to undergo 2 cardiac MRI's and fill out questionnaires 4 times. They will be asked to participate for 6 weeks with two 2-week courses (with a treatment window period of 5 days), one with ranolazine and the other with placebo (without knowing which they are taking). There is a 2-week washout period between treatments. The participants will otherwise remain on all their usual medications. The physicians will also be blinded to which medication the subject is receiving.
Participation in this study will be approximately 6 weeks, which consists of two 2-week study periods and in between a 2-week washout period:
- During the first 2-week period: Subjects will be randomized to first receive either the ranolazine or a placebo pill (sugar pill with no active medicine). Subjects will take the extended-release ranolazine or a placebo pill for a total of 2 weeks. Subjects will take 500 mg twice daily for the first 1 week and then 1000 mg twice daily for an additional 1 week. Subjects who are unable to take the higher dose due to side effects will remain on 500 mg twice daily for the entire study period. After the 2 weeks, the participant will have a Cardiac MRI and complete study questionnaires. These tools will allow us to evaluate if the participant is doing better on the medication.
- 2-week washout period: Subject will then be asked to go 2 weeks without any study medication (ranolazine or placebo).
- During the second 2-week period: Subject will then be given either extended release ranolazine or placebo depending on which was received the first time for a total of 2 weeks. Subjects will take 500 mg twice daily for the first 1 week and then 1000 mg twice daily for an additional 1 week. Subjects who are unable to take the higher dose due to side effects will remain on 500 mg twice daily for entire study period. This 2-week period will again be followed by a final Cardiac MRI and questionnaire completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranolazine | Experimental | Drug: Ranolazine147 subjects, with projected 9-10% dropout and anticipated 134 completed subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 500-1,000 mg po bid for 2 weeks with exit testing followed by cross-over to the alternate ranolazine or placebo and repeat exit testing. |
| Placebo | Placebo comparator | Drug: Placebo147 subjects, with projected 9-10% dropout and anticipated 134 completed subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 500-1,000 mg po bid for 2 weeks with exit testing followed by cross-over to the alternate ranolazine or placebo and repeat exit testing. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Men or women age >18 from diverse racial/ethnic groups;
- Competent to give informed consent;
- Patients with chronic angina or its equivalent;
- Coronary angiogram revealing MCD with no obstructive CAD (epicardial coronary stenosis <50% luminal diameter stenosis);
- Left ventricular ejection fraction > or = 45%;
Key exclusion criteria (13 listed)
- Acute coronary syndrome (defined by WHO), cardiogenic shock or requiring inotropic or intra-aortic balloon support;
- Planned percutaneous coronary intervention or CABG or established obstructive CAD with ischemia eligible for revascularization, acute MI;
- Prior non-cardiac illness with an estimated life expectancy <4 years;
- Unable to give informed consent;
- Allergy or contra-indication to CMRI testing, including renal failure, claustrophobia, and asthma, uncontrolled moderate hypertension (sitting blood pressure >160/95mmHg with measurements recorded on at least 2 occasions), conditions likely to influence outcomes: Severe lung, creatinine >1.8 or CrCl ≤ 50ml/min) or hepatic disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanolazineAlso: RanexaThis drug is approved by the U.S. Food and Drug Administration (FDA) for treatment of chronic angina. 500-1,000 mg po bid for 2 weeks | Drug | Ranolazine |
| Placebo500-1,000 mg po bid for 2 weeks | Drug | Placebo |
Primary outcome
Seattle Angina Questionnaire (SAQ)
Time frame: 2 weeks (first intervention) and 6 weeks (second intervention)
Questionnaires will be completed (SAQ - Seattle Angina Questionnaire) at the end of each treatment period. The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important.
1 secondary outcome
Cardiac Magnetic Resonance (CMRs)
Time frame: 2 weeks (first intervention) and 6 weeks (second intervention)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30293664Rambarat CA, Elgendy IY, Handberg EM, Bairey Merz CN, Wei J, Minissian MB, Nelson MD, Thomson LEJ, Berman DS, Shaw LJ, Cook-Wiens G, Pepine CJ. Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study. Int J Cardiol. 2019 Feb 1;276:8-13. doi: 10.1016/j.ijcard.2018.09.081. Epub 2018 Sep 26.
- Derived from this study: PubMed 29263019Birkeland K, Khandwalla RM, Kedan I, Shufelt CL, Mehta PK, Minissian MB, Wei J, Handberg EM, Thomson LE, Berman DS, Petersen JW, Anderson RD, Cook-Wiens G, Pepine CJ, Bairey Merz CN. Daily Activity Measured With Wearable Technology as a Novel Measurement of Treatment Effect in Patients With Coronary Microvascular Dysfunction: Substudy of a Randomized Controlled Crossover Trial. JMIR Res Protoc. 2017 Dec 20;6(12):e255. doi: 10.2196/resprot.8057.
- Derived from this study: PubMed 26614823Bairey Merz CN, Handberg EM, Shufelt CL, Mehta PK, Minissian MB, Wei J, Thomson LE, Berman DS, Shaw LJ, Petersen JW, Brown GH, Anderson RD, Shuster JJ, Cook-Wiens G, Rogatko A, Pepine CJ. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J. 2016 May 14;37(19):1504-13. doi: 10.1093/eurheartj/ehv647. Epub 2015 Nov 27.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
C. Noel Bairey Merz, MD principal investigator
Cedars-Sinai Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ranolazine in people with Microvascular Coronary Dysfunction (MCD), run by Cedars-Sinai Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seattle Angina Questionnaire (SAQ) (time frame: 2 weeks (first intervention) and 6 weeks (second intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01342029, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2019.