Efficacy of Medical Therapy in Women and Men With Angina and Myocardial Bridging

Myocardial Bridging Clinical Trial

Official title:

Efficacy of Medical Therapy in Women and Men With Angina and Myocardial Bridging

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04130438
• Other study ID #: 47447
• Status: Suspended
• Phase: Phase 2
• Start date: October 15, 2020
• Est. completion date: June 15, 2025

Study information

• Verified date: November 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposed clinical trial is relevant to public health because it is expected to expand the differential diagnosis and provide an evidence--based therapy for the large population of patients with angina in the absence of obstructive CAD who currently remain undiagnosed and untreated. It, therefore, upholds an important part of the mission of the The National Heart, Lung, and Blood Institute (NHLBI), which is to promote the treatment of heart disease and enhance the health of all individuals so that they can live longer and more fulfilling lives.

Description:

Angina in the absence of obstructive coronary artery disease (CAD) affects millions, resulting in a reduced quality of life and a burden on the health care system. Previous work has focused on endothelial and microvascular dysfunction as causes of angina in these patients, but even when these etiologies are tested for, nearly half of patients remain undiagnosed, and proven therapies are lacking. The long--term goal of this research proposal is to improve the lives of patients with angina in the absence of obstructive CAD. These patients have been found to have a disproportionate prevalence of myocardial bridges (MBs) (60% vs. 30% in the general population).

MBs are known to cause angina, and the mechanism by which they do so is also known, but MBs have not been actively studied in the context of patients with angina in the absence of obstructive CAD. Medical therapies for symptomatic MBs, including beta blockers and calcium channel blocker have been suggested, but have never been appropriately tested, and may not be better than placebo. The overall objective of this research proposal is to demonstrate that MBs are an important and treatable cause of angina in patients with non--obstructive CAD.

The investigator will conduct the first--ever randomized, double--blind, placebo--controlled trial of medical therapy in patients with angina and an MB. The rationale is that a proven treatment would significantly expand the paradigm by which patients with angina in the absence of obstructive CAD are evaluated and treated. Our central hypothesis is that beta blockers and calcium channel blockers are effective treatments for reducing angina in patients with an MB compared with placebo. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine the efficacy of beta blockers and calcium channel blockers in treating patients with angina and an MB and 2) Identify predictors of efficacy of beta blockers and calcium channel blockers in treating patients with angina and an MB. For Aim #1, the investigator will randomize a total of 360 adult patients with angina and an MB into one of three treatment arms: beta blocker (nebivolol), calcium channel blocker (diltiazem), or placebo (1:1:1).

Efficacy will be determined after 30 days on the study drug by a change in angina, as assessed by the Seattle Angina Questionnaire (SAQ). The investigator will also evaluate changes in exercise capacity, as well as drug adherence and side effects. For Aim #2, the investigator will evaluate MB muscle index (MMI, a product of MB length x depth) by coronary computed tomography angiography, as well as male sex, as predictors of efficacy. Randomization will be stratified on sex, ensuring a balance of women and men in each arm. The proposed research is innovative because it shifts the current clinical perspective on angina in the absence of obstructive CAD by considering myocardial bridging as a potential etiology.

It is also significant because it will substantially increase the number of patients with angina in the absence of obstructive CAD that clinicians are able to diagnose and treat, ultimately leading to improvements in quality of life and a reduction in health care costs.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 360
• Est. completion date: June 15, 2025
• Est. primary completion date: January 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria

1. Age =18 years

2. Stable angina (typical or atypical, based on Diamond criteria (35))

3. Exercise stress echocardiogram or exercise stress test (with beta blocker or calcium channel blocker held) performed within six months of enrollment

4. CCTA or invasive coronary angiogram confirming the presence of an MB

5. Absence of obstructive CAD, as demonstrated by no ischemia on stress testing and no significant obstructive CAD (coronary stenosis <50%) on CCTA or invasive coronary angiogram

Exclusion Criteria:

1. Asymptomatic

2. Status--post heart transplant

3. Presence of another likely explanation of chest pain, such as pulmonary hypertension, hypertrophic obstructive cardiomyopathy, or aortic stenosis

4. Presence of an acute coronary syndrome (unstable angina, NSTEMI, or STEMI), Tako--tsubo, or cardiogenic shock

5. An abnormal left ventricular ejection fraction (EF<55%)

6. History of a severe adverse reaction to beta blockers or calcium channel blockers (prior minor intolerance or ineffectiveness not exclusion)

7. Use of existing medication that has an unsafe drug--drug interaction with beta blockers or calcium channel blockers

8. Refusal to take beta blockers or calcium channel blockers

9. Resting systolic blood pressure <100 mmHg or heart rate <50 beats per minute

10. Inability to provide an informed consent, including an inability to speak, read, or understand English or Spanish

11. A hearing impairment that won't allow for a typical verbal conversation or a visual impairment that won't allow for reading of the written consent

12. A potentially vulnerable subject (including pregnant women, prisoners, economically and educationally disadvantaged, decisionally impaired, and institutionalized individuals)

Related Conditions & MeSH terms

• Myocardial Bridging

Intervention

Drug:
• Nebivolol
The intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days.
• Diltiazem
The intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days.

Other:
• Placebo
The intervention to be tested is oral beta blocker (nebivolol 2.5 mg) vs. calcium channel blocker (Diltiazem-SR 120 mg) vs. placebo. Once enrolled, baseline data will be gathered and subjects will be randomly assigned to a treatment arm. Subjects will be instructed to take their assigned study drug once a day for 30 days.

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Drug adherence.	This will be measured by pill count at the end of 30 days.	30 days
Other	Side effects.	These will be self-reported side effects recorded in a diary to be turned in at 30 days. In addition, patients are requested to contact us regarding any serious side effects during the study. Finally, we will also ask the patient of any side effects during their 30-day follow-up to ensure that we've captured any symptoms.	30 days
Primary	Effectiveness of beta blockers and calcium channel blockers for reducing angina in patients with a Myocardial Bridge (MB) compared to placebo	The study will randomize a total of 360 adult patients with angina and an MB into one of three treatment arms: beta blocker (nebivolol), calcium channel blocker (diltiazem), or placebo (1:1:1). Efficacy will be determined after 30 days on the study drug by a change in angina, as assessed by the Seattle Angina Questionnaire (SAQ).	6 months
Secondary	Changes in exercise capacity.	Changes in exercise capacity will be measured by difference in exercise time increment between the groups. The Duke treadmill score is calculated as exercise time × (5 × ST-segment deviation) - (4 × exercise angina), with 0 = no angina, 1 = non-limiting angina, and 2 = exercise-limiting angina. Scores will be categorized as low risk (=+5), moderate risk (-10 to +4) and high risk (=-11).; Ref: L.J. Shaw, E.D. Peterson, L.K. Shaw, K.L. Kesler, E.R. Delong, F.E. Harrell Jr., L.H. Muhlbaier, D.B. Mark. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation, 98 (1998), pp. 1622-1630	30 days
Secondary	Changes in exercise capacity.	We will also calculate the Duke Treadmill Score for each patient and compare this between groups.	30 days