Efficacy of Targeted Medical Therapy in Angina and Nonobstructive Coronary Arteries (MVP-ANOCA)

A Randomized Controlled Study of Targeted Medical Therapy Versus Placebo for Angina and Non- Obstructive Coronary Arteries: The MVP-ANOCA Study

The goal of this clinical trial is to learn if targeted medical therapy will improve symptoms and quality of life in patients with angina and non-obstructive coronary arteries compared to placebo, after the underlying cause of the chest pain has been ascertained by coronary function testing.

Participants will be treated with either medications that target the underlying cause of their chest pain or placebo for 4 weeks after a drug titration phase of 1-3 weeks. They will be asked to complete a series of questionnaires to evaluate their quality of life at the beginning and end of the study.

Study Overview

• Status: Recruiting
• Conditions: Angina Pectoris; Microvascular Angina; Vasospastic Angina; Myocardial Bridge of Coronary Artery
• Intervention / Treatment: Drug: Amlodipine; Drug: Nebivolol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Christopher Wong, MBBS, PhD; Phone Number: (650) 725 5909; Email: ccywong@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Hospital
      • Principal Investigator: Jennifer Tremmel, MD
      • Contact: Christopher Wong, MBBS, PhD; Phone Number: 650-725-5909; Email: ccywong@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients with stable angina referred to the Stanford University Hospital cardiac catheterization laboratory for clinically indicated coronary function testing are eligible for inclusion into the study.

Specific inclusion criteria for randomization:

• Absence of significant epicardial coronary artery disease on angiography
• Fractional flow reserve > 0.80

And ≥ 1 of the following:

• Epicardial coronary spasm on acetylcholine testing
• Microvascular spasm on acetylcholine testing
• Coronary flow reserve < 2.5
• Index of microcirculatory resistance ≥ 25
• Myocardial bridge on intravascular ultrasound with dobutamine resting full-cycle ratio ≤ 0.76

Exclusion Criteria:

• Acute coronary syndrome less than one week prior to enrolment
• Cardiomyopathy
• Contraindications to beta-blockers or calcium channel blockers
• Baseline systolic blood pressure < 95 mmHg
• Baseline heart rate < 55 bpm

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Targeted medical therapy; Epicardial or microvascular coronary spasm: Amlodipine 2.5mg initial dose, 10mg max dose; Coronary microvascular dysfunction: Nebivolol 5mg initial dose, 20mg max dose; Myocardial Bridge: Nebivolol 5mg initial dose, 20mg max dose; Mixed epicardial/microvascular spasm and coronary microvascular dysfunction/myocardial bridge: Amlodipine 2.5mg initial dose, 10mg max dose; PLUS Nebivolol 5mg initial dose, 20mg max dose Participants will take their assigned therapy after randomization. Weekly person via in-person visit or telephone is performed to uptitrate therapy to the maximally tolerated dose. After 1-3 weeks, the initial drug titration phase is completed and a final dose reached. Participants are then instructed to take the maximally tolerated dose for an additional 4 weeks to the conclusion of the study.	Drug: Amlodipine; Amlodipine taken once orally daily at a starting dose of 2.5mg, uptitrated to a maximum of 10mg if tolerated.; Other Names: Norvasc; Katerzia; Norliqva; Drug: Nebivolol; Nebivolol taken once orally daily at a starting dose of 5mg, uptitrated to a maximum of 20mg if tolerated.; Other Names: Bystolic
Placebo Comparator: Placebo; Epicardial or microvascular coronary spasm: Placebo; Coronary microvascular dysfunction: Placebo; Myocardial Bridge: Placebo; Mixed epicardial/microvascular spasm and coronary microvascular dysfunction/myocardial bridge: Placebo Participants will take their assigned therapy after randomization. Weekly person via in-person visit or telephone is performed to uptitrate therapy to the maximally tolerated dose. After 1-3 weeks, the initial drug titration phase is completed and a final dose reached. Participants are then instructed to take the maximally tolerated dose for an additional 4 weeks to the conclusion of the study.	Drug: Placebo; Placebo taken once orally daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seattle Angina Questionnaire summary score	Change in Seattle Angina Questionnaire summary score at follow-up compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints	Incidence of bleeding, coronary dissection, stroke, periprocedural myocardial infarction, non-self-limiting arrhythmias during the index coronary function testing procedure	Baseline
EuroQol 5 dimension - 5L index score	Change in EuroQol 5 dimension score - 5L index score at follow-up compared to baseline. The index ranges from -0.573 to 1.000, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
EuroQol 5 dimension - 5L visual analogue score	Change in EuroQol 5 dimension score - 5L visual analogue score at follow-up compared to baseline. The index ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
PHQ-4 score	Change in PHQ-4 at follow-up compared to baseline. The score ranges from 0 - 12, with a higher score indicating a worse outcome.	5-7 weeks (depending on drug titration period)
Treatment Satisfaction Questionnaire for Medication score	Change in Treatment Satisfaction Questionnaire for Medication score at follow-up compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
Seattle Angina Questionnaire summary score stratified by specific chest pain endotypes	Change in Seattle Angina Questionnaire summary score stratified by specific chest pain endotypes at follow-up compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
EuroQol 5 dimension - 5L index score stratified by specific chest pain endotypes	EuroQol 5 dimension - 5L index score stratified by specific chest pain endotypes at follow-up compared to baseline. The index ranges from -0.573 to 1.000, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
EuroQol 5 dimensions - 5L visual analogue score stratified by specific chest pain endotypes	EuroQol 5 dimensions - 5L visual analogue score stratified by specific chest pain endotypes at follow-up compared to baseline. The index ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
PHQ-4 scores stratified by specific chest pain endotypes	PHQ-4 score stratified by specific chest pain endotypes at follow-up compared to baseline. The score ranges from 0 - 12, with a higher score indicating a worse outcome.	5-7 weeks (depending on drug titration period)
Treatment Satisfaction Questionnaire for Medication score stratified by specific chest pain endotypes	Treatment Satisfaction Questionnaire for Medication scores stratified by specific chest pain endotypes at follow-up compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
Seattle Angina Questionnaire summary score stratified by baseline angina frequency	Change in Seattle Angina Questionnaire summary score stratified by baseline angina frequency at at follow-up compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.	5-7 weeks (depending on drug titration period)
Proportion of patients with good response, no angina, and excellent health status	Difference between targeted medical therapy group and placebo group in proportion of patients with good response (Seattle Angina Questionnaire summary score ≥ 10), no angina (Seattle Angina Questionnaire angina frequency score = 100), and excellent health status (Seattle Angina Questionnaire summary score ≥ 75).	5-7 weeks (depending on drug titration period)
Major adverse cardiac events	Difference between targeted medical therapy group and placebo group in incidence of cardiac death, myocardial infarction, and hospital presentation for unstable angina.	5-7 weeks (depending on drug titration period)

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Jennifer Tremmel, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 12, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 22, 2024

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Myocardial Ischemia; Chest Pain; Angina, Unstable; Coronary Vessel Anomalies; Angina Pectoris; Microvascular Angina; Angina Pectoris, Variant; Myocardial Bridging; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Adrenergic Agonists; Adrenergic Agents; Adrenergic beta-Agonists; Calcium Channel Blockers; Vasodilator Agents; Antihypertensive Agents; Adrenergic beta-1 Receptor Agonists; Nebivolol; Amlodipine
• Other Study ID Numbers: IRB-75085; 24POST1189688 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes