Targeted Medical Therapy for Angina

(MVP-ANOCA Trial)

Overseen By Christopher Wong, MBBS, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Stanford University

Must not be taking: Beta-blockers, Calcium channel blockers

Disqualifiers: Acute coronary syndrome, Cardiomyopathy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if targeted medications can improve symptoms and quality of life for people with angina who have non-blocked coronary arteries. Participants will receive either specific medications, such as Amlodipine (a calcium channel blocker) or Nebivolol (a beta-blocker), or a placebo. This trial suits those with stable angina who have been referred for heart tests at Stanford and have certain heart conditions without significant artery blockage. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in a larger group and represents the final step before FDA approval. Participants have the opportunity to contribute to potentially groundbreaking advancements in angina treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that amlodipine was generally well-tolerated by patients. It is commonly used to treat high blood pressure and chest pain, with most people experiencing only mild side effects like dizziness or ankle swelling.

Research has shown that nebivolol, another medication in this trial, also has a good safety record. It helps relax blood vessels, which can reduce chest pain. Some common side effects include headache and tiredness, but these are usually mild.

Both amlodipine and nebivolol have FDA approval for other uses, indicating their safety. However, since reactions can vary, discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for angina because they offer a tailored approach to managing different types of coronary issues. Unlike standard treatments that often involve general medications like nitrates, beta-blockers, or calcium channel blockers, this study uses Amlodipine and Nebivolol in a targeted way. Amlodipine, a calcium channel blocker, is specifically used here for coronary spasms, while Nebivolol, a beta-blocker, targets microvascular dysfunction and myocardial bridges. This precision in addressing specific coronary problems could lead to more effective management and improved outcomes for patients with angina.

What evidence suggests that this trial's treatments could be effective for angina?

Research has shown that amlodipine, one of the treatments in this trial, can significantly reduce the frequency of angina, or chest pain. One study found that patients taking amlodipine experienced fewer chest pain episodes than those taking a placebo, which contains no active medicine. Nebivolol, another treatment option in this trial, improves blood flow and has unique properties that can alleviate chest pain. In trials, patients using nebivolol reported better control over their chest pain and an improved quality of life. Both medications work by relaxing and widening blood vessels, which increases blood flow and reduces chest pain in people with angina. ^{6 7 8 9 10}

Who Is on the Research Team?

Jennifer Tremmel, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for patients with different types of chest pain (angina) linked to heart issues without blocked arteries. They should have undergone tests confirming the cause of their angina. People who can't take part include those with other significant health problems, pregnant women, or individuals currently on certain medications.

Inclusion Criteria

Fractional flow reserve > 0.80

Absence of significant epicardial coronary artery disease on angiography

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.

Exclusion Criteria

Baseline systolic blood pressure < 95 mmHg

I cannot take beta-blockers or calcium channel blockers due to health reasons.

I have not had a heart attack or severe heart issue in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Drug Titration

Participants undergo a drug titration phase to reach the maximally tolerated dose

1-3 weeks

Weekly visits (in-person or telephone)

Treatment

Participants receive the assigned therapy or placebo for 4 weeks

4 weeks

Weekly visits (in-person or telephone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amlodipine
• Nebivolol

Trial Overview

The study aims to see if targeted drugs like Amlodipine and Nebivolol can help improve symptoms and life quality in angina patients compared to a placebo. Participants will be randomly given either medication or a placebo for 50 days while monitoring their well-being through questionnaires.

How Is the Trial Designed?

Group I: Targeted medical therapy Experimental Treatment 2 Interventions

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Amlodipine is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Norvasc for:

• Hypertension
• Angina
• Variant angina

Approved in European Union as Norvasc for:

• Hypertension
• Coronary artery disease
• Variant angina

Approved in Canada as Norvasc for:

• Hypertension
• Angina

Approved in Japan as Norvasc for:

• Hypertension
• Angina pectoris

Approved in China as Norvasc for:

• Hypertension

Approved in Switzerland as Norvasc for:

• Hypertension
• Coronary artery disease

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Published Research Related to This Trial

Nebivolol is a selective beta1-adrenergic blocker that not only lowers blood pressure but also enhances nitric oxide availability, leading to improved blood vessel function and reduced vascular resistance, making it effective for treating hypertension and heart failure.

Clinical studies indicate that long-term use of nebivolol improves heart function, exercise capacity, and reduces hospital admissions for cardiovascular issues, particularly in elderly patients and high-risk populations like African Americans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebivolol in the treatment of chronic heart failure. Veverka, A., Salinas, JL.[2022]

In a study of 1468 patients with mild to moderate hypertension, nebivolol significantly improved blood pressure control, with 27% of patients reaching target BP after 4 weeks and 45% after 8 weeks.

Nebivolol also enhanced quality of life (QoL) by an average of 9-10 points after 8 weeks, regardless of whether it was used as monotherapy, an add-on, or a switch medication, suggesting its effectiveness and tolerability in treating hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life and efficacy of nebivolol in an open-label study in hypertensive patients. the QoLaN study. Hermans, MP., De Coster, O., Seidel, L., et al.[2015]

Nebivolol is a third-generation beta-adrenergic blocker with unique vasodilatory properties, making it effective in lowering blood pressure and providing additional cardiovascular benefits.

In a long-term trial, nebivolol significantly reduced death and hospital admissions for cardiovascular causes in heart failure patients compared to placebo, indicating its potential as a beneficial treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebivolol: a third-generation beta-adrenergic blocker. Veverka, A., Nuzum, DS., Jolly, JL.[2015]

Nebivolol is an effective beta-blocker for lowering blood pressure, showing similar efficacy to other antihypertensive medications like atenolol and lisinopril, based on 12 clinical trials.

In heart failure patients, nebivolol was associated with a significant 14% reduction in all-cause mortality and cardiovascular hospitalization over 12 months, indicating potential benefits beyond blood pressure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebivolol: a third-generation beta-blocker for hypertension. Cheng, JW.[2015]

Nebivolol, a β(1)-selective β-blocker, significantly reduced diastolic blood pressure (up to 11.1 mm Hg) and systolic blood pressure (up to 12.4 mm Hg) compared to placebo in a pooled analysis of 3 trials involving 1811 patients over 12 weeks.

The treatment was generally well tolerated, with common side effects including headache and fatigue, and its efficacy was consistent across different demographics, including black patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of nebivolol in stage I-II hypertension: a pooled analysis of data from three randomized, placebo-controlled monotherapy trials. Weiss, RJ., Saunders, E., Greathouse, M.[2015]

Nebivolol, a beta-blocker under FDA review for hypertension, effectively reduces blood pressure and has a unique mechanism that includes nitric oxide-mediated vasodilation, making it comparable to other common antihypertensive medications.

In elderly patients with stable congestive heart failure, nebivolol improved survival and reduced hospital admissions compared to placebo, suggesting it could be a beneficial treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebivolol: new therapy update. Sule, SS., Frishman, W.[2015]

In a 9-month study involving 845 patients with stage I to II hypertension, nebivolol demonstrated significant long-term antihypertensive effects, reducing diastolic blood pressure by an average of 15.0 mm Hg and systolic blood pressure by 14.8 mm Hg, with over 78% of patients responding positively to the treatment.

Nebivolol was found to be safe and well-tolerated, with the incidence of adverse events comparable to earlier studies and decreasing over time, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Nebivolol monotherapy versus Nebivolol in combination with other antihypertensive therapies for the treatment of hypertension. Papademetriou, V.[2015]

In a study of 51 hypertensive patients with vasospastic angina, both nebivolol and diltiazem significantly reduced coronary vasospasm over a 12-week period, but diltiazem was more effective than nebivolol.

Quality of life, as measured by the Seattle Angina Questionnaire, improved for all patients, but there were no significant differences in quality of life or blood pressure changes among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of nebivolol versus diltiazem in improving coronary artery spasm and quality of life in patients with hypertension and vasospastic angina: A prospective, randomized, double-blind pilot study. Kook, H., Hong, SJ., Yang, KS., et al.[2020]

Nebivolol is a unique β1-adrenergic receptor antagonist that not only lowers blood pressure through selective β1 blockade but also promotes vasodilation via nitric oxide production, making it different from other β-blockers.

Clinical studies show that nebivolol is effective in reducing blood pressure with a low incidence of side effects, and it may also benefit patients with erectile dysfunction caused by other β-blockers, supporting its use in hypertension and heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Nebivolol Pharmacology and Clinical Evidence. Fongemie, J., Felix-Getzik, E.[2018]

Nebivolol is a highly selective β(1)-blocker that not only treats hypertension but also has a unique ability to increase nitric oxide levels, leading to vasodilation, which may benefit patients with heart failure.

Clinical trials indicate that nebivolol improves heart function and reduces morbidity and mortality in heart failure patients compared to placebo, although its effects are not as strong as those of other recommended β-blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebivolol for the treatment of heart failure. Dery, AS., Hamilton, LA., Starr, JA.[2019]

In a study of 2112 elderly heart failure patients (average age 76.1 years), nebivolol was found to be safe and effective, showing similar efficacy across different levels of kidney function (eGFR).

Nebivolol did not present major safety concerns in patients with moderate renal impairment, although there were higher rates of discontinuation due to bradycardia, indicating it can be a viable treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial. Cohen-Solal, A., Kotecha, D., van Veldhuisen, DJ., et al.[2021]

In a study involving 6,376 patients over six weeks, Nebivolol effectively reduced systolic blood pressure by an average of 29 mm Hg and diastolic blood pressure by 16 mm Hg, with 62.2% of patients achieving normalized diastolic blood pressure.

Nebivolol was found to be safe and well-tolerated, also leading to significant reductions in cholesterol and triglycerides, particularly in diabetic patients, suggesting additional cardiovascular benefits beyond blood pressure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nebivolol, a beta blocker of the 3rd generation: modern therapy of arterial hypertension. Results of a multicenter observation study]. von Fallois, J., Faulhaber, HD.[2019]

Nebivolol HCl transferosomal transdermal patches were developed to improve drug delivery and reduce gastrointestinal side effects associated with oral administration, showing promising results in enhancing drug permeation through the skin.

The optimized transferosomal formulations demonstrated superior drug permeation compared to traditional patches, with stability studies indicating that these patches could be a viable option for managing hypertension effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fabrication, Optimization, and Evaluation of Transdermal Patch: As an Alternative and Effective Transdermal Delivery System for Nebivolol HCl. Birkodi, S., Patil, AS., Masareddy, R., et al.[2023]

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