Trial Outcomes & Findings for Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia (NCT NCT01342029)

NCT ID: NCT01342029

Last Updated: 2019-04-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

142 participants

Primary outcome timeframe

2 weeks (first intervention) and 6 weeks (second intervention)

Results posted on

2019-04-24

Participant Flow

Participant milestones

Participant milestones
Measure	Ranolazine First, Then Placebo 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. Ranolazine: 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	Placebo First, Then Ranolazine 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. Placebo: 500-1,000 mg po bid for 2 weeks
Period 1 STARTED	70	72
Period 1 Dropout	3	1
Period 1 COMPLETED	67	71
Period 1 NOT COMPLETED	3	1
Washout STARTED	67	71
Washout COMPLETED	67	67
Washout NOT COMPLETED	0	4
Period 2 STARTED	67	67
Period 2 Dropout	2	0
Period 2 COMPLETED	65	67
Period 2 NOT COMPLETED	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranolazine/Placebo n=142 Participants 147 subjects will be enrolled at two clinical sites, with projected 9-10% dropout and anticipated 134 completed subjects. For Ranolazine first group, 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. For Placebo first group, 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	142 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	55.2 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Region of Enrollment United States	142 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 weeks (first intervention) and 6 weeks (second intervention)

Population: Not all participants answered every question in the SAQ, thus the numbers are different for each question.

Outcome measures

Outcome measures
Measure	Ranolazine n=128 Participants 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. Ranolazine: 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	Placebo n=128 Participants 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. Placebo: 500-1,000 mg po bid for 2 weeks
Seattle Angina Questionnaire (SAQ) Physical Limitation	68.09 Units on scale Standard Deviation 23.34	66.7 Units on scale Standard Deviation 23.34
Seattle Angina Questionnaire (SAQ) Angina Stability	58.4 Units on scale Standard Deviation 26.11	51.17 Units on scale Standard Deviation 27.68
Seattle Angina Questionnaire (SAQ) Angina Frequency	63.91 Units on scale Standard Deviation 26.09	62.73 Units on scale Standard Deviation 25.95
Seattle Angina Questionnaire (SAQ) Treatment Satisfaction	74.16 Units on scale Standard Deviation 21.23	74.17 Units on scale Standard Deviation 21.08
Seattle Angina Questionnaire (SAQ) Quality of Life	56.05 Units on scale Standard Deviation 23.09	54.17 Units on scale Standard Deviation 23.31
Seattle Angina Questionnaire (SAQ) SAQ Overall	62.49 Units on scale Standard Deviation 19.32	60.97 Units on scale Standard Deviation 20.11

SECONDARY outcome

Timeframe: 2 weeks (first intervention) and 6 weeks (second intervention)

Population: Out of 142 randomized, there were 10 dropouts and 4 missing treatment periods. Therefore 128 was included in analysis

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.

Outcome measures

Outcome measures
Measure	Ranolazine n=128 Participants 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. Ranolazine: 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	Placebo n=128 Participants 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. Placebo: 500-1,000 mg po bid for 2 weeks
Cardiac Magnetic Resonance (CMRs)	1.98 myocardial perfusion reserve index Standard Deviation 0.46	1.96 myocardial perfusion reserve index Standard Deviation 0.42

Adverse Events

Ranolazine

Serious events: 6 serious events

Other events: 8 other events

Deaths: 14 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 11 deaths

Serious adverse events

Serious adverse events
Measure	Ranolazine n=142 participants at risk 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. Ranolazine: 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 Placebo: 500-1,000 mg po bid for 2 weeks	Placebo n=142 participants at risk 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. Ranolazine: 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 Placebo: 500-1,000 mg po bid for 2 weeks
Cardiac disorders NSTEMI	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Bronchospasm	100.0% 1/1 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Chest pain, dizziness, and pre-syncope	1.4% 2/142 • Number of events 2 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders syncope	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Chest pain	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Bradycardia	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.

Other adverse events

Other adverse events
Measure	Ranolazine n=142 participants at risk 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. Ranolazine: 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 Placebo: 500-1,000 mg po bid for 2 weeks	Placebo n=142 participants at risk 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. Ranolazine: 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 Placebo: 500-1,000 mg po bid for 2 weeks
General disorders Nausea and dizziness	2.1% 3/142 • Number of events 3 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Nervous system disorders Arm shaking	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
General disorders Back pain	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Endocrine disorders Renal change	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
General disorders Throat pain, swelling and tightness	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Endocrine disorders Rectocele	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
General disorders cough	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Sinus infection	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders chest pain	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	2.8% 4/142 • Number of events 4 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Excessive Sweating	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Blood and lymphatic system disorders Hematemesis	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.
Cardiac disorders Palpitations and Afib	0.00% 0/142 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.	0.70% 1/142 • Number of events 1 • 6 weeks The SAEs are based on the publication which represent all SAEs throughout the study.

Additional Information

C.Noel Bairey Merz, MD

Cedars-Sinai Medical Center

Phone: 310-423-9680

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place