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RecruitingNCT06424834MVP-ANOCAUpdated Nov 27, 2024

Efficacy of Targeted Medical Therapy in Angina and Nonobstructive Coronary Arteries

A Phase 2/3 interventional study of Amlodipine and Nebivolol in Angina Pectoris, Microvascular Angina and Vasospastic Angina, sponsored by Stanford University. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-27.

Sponsored by Stanford University · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Angina Pectoris
  • Microvascular Angina
  • Vasospastic Angina
  • Myocardial Bridge of Coronary Artery
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
150 participants (estimated)

Study arms

  • Experimental
    Targeted medical therapy

    1. Epicardial or microvascular coronary spasm: Amlodipine 2.5mg initial dose, 10mg max dose 2. Coronary microvascular dysfunction: Nebivolol 5mg initial dose, 20mg max dose 3. Myocardial Bridge: Nebivolol 5mg initial dose, 20mg max dose 4. 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 · Drug: Nebivolol

  • Placebo comparator
    Placebo

    1. Epicardial or microvascular coronary spasm: Placebo 2. Coronary microvascular dysfunction: Placebo 3. Myocardial Bridge: Placebo 4. 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

Interventions

  • DrugAmlodipine

    Amlodipine taken once orally daily at a starting dose of 2.5mg, uptitrated to a maximum of 10mg if tolerated.

    Also known as: Norvasc, Katerzia, Norliqva

  • DrugNebivolol

    Nebivolol taken once orally daily at a starting dose of 5mg, uptitrated to a maximum of 20mg if tolerated.

    Also known as: Bystolic

  • DrugPlacebo

    Placebo taken once orally daily.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

Secondary outcomes

  1. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  2. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  3. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  4. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  5. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  6. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  7. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  8. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  9. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  10. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

  11. 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).

    Time frame: 5-7 weeks (depending on drug titration period)

  12. Safety endpoints

    Incidence of bleeding, coronary dissection, stroke, periprocedural myocardial infarction, non-self-limiting arrhythmias during the index coronary function testing procedure

    Time frame: Baseline

  13. 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.

    Time frame: 5-7 weeks (depending on drug titration period)

06

Study locations

1 of 1 sites recruiting
  • Stanford Hospital
    Palo Alto, California 94304, United States
    • Christopher Wong, MBBS, PhD · Contact · ccywong@stanford.edu · 650-725-5909
    • Jennifer Tremmel, MD · Principal investigator
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06424834
Lead sponsor
Stanford University
Collaborators
American Heart Association
Responsible party
Christopher Chi-Yuen Wong (Postdoc, Stanford University) — Principal investigator
First posted
May 22, 2024
Start date
Oct 10, 2024
Primary completion
Dec 2026 (estimated)
Completion
Dec 2026 (estimated)
Last update
Nov 27, 2024

Study contacts

Christopher Wong, MBBS, PhD
Contact
ccywong@stanford.edu
(650) 725 5909
Jennifer Tremmel, MD
principal investigator · Stanford University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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