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

NCT ID: NCT04130438

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-15
• Study Completion Date: 2024-10-17

Brief 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.

Detailed 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.

Conditions

Myocardial Bridging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Beta Blocker (nebivolol)

Group Type: ACTIVE_COMPARATOR

Nebivolol

Intervention Type: DRUG

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.

Calcium Channel Blocker (diltiazem)

Group Type: ACTIVE_COMPARATOR

Diltiazem

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Jennifer A Tremmel, MD, MS

Interventional cardiologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer Tremmel, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Countries

United States

References

Shaw LJ, Peterson ED, Shaw LK, Kesler KL, DeLong ER, Harrell FE Jr, Muhlbaier LH, Mark DB. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation. 1998 Oct 20;98(16):1622-30. doi: 10.1161/01.cir.98.16.1622.

Reference Type: BACKGROUND

PMID: 9778327 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

47447

Identifier Type: -

Identifier Source: org_study_id