Nebivolol ANOCA Treatment Randomized Trial

NCT ID: NCT06755801

Last Updated: 2025-01-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-09-30

Brief Summary

To determine the effectiveness of the beta-blocker nebivolol in controlling symptoms and improving the quality of life in patients with angina and coronary microvascular dysfunction.

Detailed Description

Objective To determine the effectiveness of the beta-blocker nebivolol in controlling symptoms and improving the quality of life in patients with angina and coronary microvascular dysfunction.

Hypothesis Treatment with titrated nebivolol will result superior to placebo in symptoms control in patients presenting with coronary microvascular disease (CMD).

Study design Prospective, multicenter, controlled, double-blinded, randomized clinical trial.

Inclusion criteria • Patients over 18 years old with symptoms or evidence of myocardial ischemia and coronary arteries without lesions or with epicardial lesions (<50% by visual estimation or FFR >0.80 / RFR >0.90), and

• CFR ≤ 2.0 and/or IMR≥25 Exclusion criteria Life expectancy <1 year, inability to provide informed consent, severe valve disease, left ventricular ejection fraction <30%, clinical contraindication for betablockers treatment.

Treatment arms Randomization will be performed after invasive diagnostic of CMD:

Study group: Nebivolol • Patients will start with a dose of 5 mg every 24 hours. Biweekly dose adjustments will be performed during the first two months, increasing the dose (if tolerated with respect to heart rate, blood pressure, and symptoms) up to a maximum of 20 mg/24 hours.

Control group: Placebo

• Patients will be treated with one tablet every 24 hours. Primary endpoint: The effectiveness of nebivolol treatment in improving angina symptoms was measured using the SAQ questionnaire after 6 months of treatment.

Secondary endpoints • Quality of life at 6 months.

• Functional capacity at 6 months.
• Major cardiac events at 1 year.

Conditions

ANOCA - Angina With Non-obstructive Coronary Arteries; Coronary Microvascular Dysfunction (CMD)

Study Design

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

Study Groups

Active treatment group

Nevibolol tratment

Group Type: EXPERIMENTAL

Nevibolol

Intervention Type: DRUG

Beta-blockers are the first-line treatment for patients with stable angina secondary to classic epicardial atherosclerotic disease, where their clinical benefits are well-established (4). However, their efficacy has not yet been demonstrated in ANOCA patients with MVD, where beta-blockers are frequently used due to their physiological plausibility. Beta-blockers act by competitively inhibiting catecholamine receptors. The therapeutic benefits of beta-blockade in patients with stable angina are mediated by a reduction in myocardial oxygen demand. Myocardial oxygen demand depends on heart rate, contractility, and left ventricular wall tension, all of which are reduced with beta-adrenergic blockade. The reduction in wall tension is partly mediated by the antihypertensive action of these drugs. The decrease in heart rate occurs both at rest and during sympathetic activation such as exercise or stress. The negative inotropic effect of these drugs also contributes to reducing myocardial oxyg

Control group

Placebo group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Nevibolol

Beta-blockers are the first-line treatment for patients with stable angina secondary to classic epicardial atherosclerotic disease, where their clinical benefits are well-established (4). However, their efficacy has not yet been demonstrated in ANOCA patients with MVD, where beta-blockers are frequently used due to their physiological plausibility. Beta-blockers act by competitively inhibiting catecholamine receptors. The therapeutic benefits of beta-blockade in patients with stable angina are mediated by a reduction in myocardial oxygen demand. Myocardial oxygen demand depends on heart rate, contractility, and left ventricular wall tension, all of which are reduced with beta-adrenergic blockade. The reduction in wall tension is partly mediated by the antihypertensive action of these drugs. The decrease in heart rate occurs both at rest and during sympathetic activation such as exercise or stress. The negative inotropic effect of these drugs also contributes to reducing myocardial oxyg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18 years or older.

• Presence of stable angina symptoms, defined as compatible symptoms occurring at least once weekly in the last three months.
• Absence of functionally significant epicardial coronary artery disease (FFR > 0.80).
• Microvascular functional study showing CFR< 2,0 and/or IMR ≥ 25.

Exclusion Criteria

• Allergy or contraindication to the use of beta-blockers.
• Indication for beta-blocker treatment due to another pathology.
• Ventricular dysfunction (LVEF < 45%).
• Percutaneous coronary revascularization in the last 6 months.
• History of surgical revascularization.
• First-degree atrioventricular block or bifascicular block.
• Presence of hemodynamically significant valvulopathy.
• Presence of cardiomyopathy or congenital cardiac anomaly.
• Severe renal insufficiency (eGFR < 30 ml/min).
• Liver failure (history of cirrhosis or transaminase elevation > 3 times the upper limit of normal).
• Pregnant or lactating women.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spanish Society of Cardiology

OTHER

Sponsor Role: lead

Responsible Party

Fernando Alfonso

Head of Cardiology Department. H. U. de la Princesa.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

FERNANDO RIVERO, MD,PHD

Role: CONTACT

hemodinamicaprincesa@gmail.com

+34 915202470.

Other Identifiers

sec1589634

Identifier Type: -

Identifier Source: org_study_id