Evaluation of the Efficacy of MACitentan in the Treatment of CoronaryMICrovascular Angina (MACMIC)

Early Phase 1

Recruiting

• Conditions: Coronary Microvascular Angina; Macitentan
• Interventions: Drug: Macitentan 10 mg tablet, once daily.

• Registration Number: NCT06811831
• Lead Sponsor: China-Japan Friendship Hospital

Brief Summary

Coronary microvascular angina (MVA) significantly reduces quality of life and increases the risk of heart problems in patients with angina. Unfortunately, there are no effective treatments available yet. The endothelin-1 (ET-1) - endothelin receptor (ETRs) system plays a critical role in MVA. Preclinical studies demonstrate that ETRs antagonists or pericyte-specific knockdown of ETRs can improve coronary microvascular function in myocardial ischemia/reperfusion mice and diabetic mice. Foreign clinical drug trials have shown that ETRs antagonists may alleviate patients' symptoms. However, these studies predominantly rely on conventional coronary angiography rather than direct assessment of coronary microvascular function. Early experimental trials using ETRs antagonists reported a high incidence of side effects, such as sodium retention and headaches, which negatively impacted treatment satisfaction.

To address these limitations, a pilot study is proposed to evaluate the efficacy of macitentan in MVA treatment. This investigation will implement thermodilution-based coronary microcirculation function testing to precisely characterize the severity and subtype of coronary microvascular lesions in MVA patients. By administering macitentan - a safer ETRs antagonist - the study aims to systematically assess improvements in coronary microvascular function, angina symptom relief, and adverse event incidence. The findings are expected to provide critical evidence regarding the therapeutic potential and safety profile of macitentan, while establishing foundational data for subsequent large-scale clinical trials.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-11-01
• Status Verified: 2025-01
• Study First Submitted: 2025-01-22
• Study First Submitted QC: 2025-02-01
• Last Update Submitted: 2025-02-01
• Study First Posted: 2025-02-06
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-10-01
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Age 18-75 years old.
• With typical angina symptoms.
• Excluding obstructive coronary lesions (coronary stenosis ≤50% or FFR ≥0.8) by CAG.
• Coronary microcirculatory function CFR<2.5 and/or IMR>25 assessed by temperature dilution method.

Exclusion Criteria

• Pregnant or lactating women.
• History of heart attack within the last 90 days.
• Severe heart disease (e.g., moderate to severe heart failure, severe heart valve disease).
• Severe renal impairment (GFR <30 ml/min/1.73m2).
• Severe liver disease (Child-Pugh class C).
• Moderately severe anaemia (haemoglobin concentration <90 g/L).
• Participation in another drug intervention trial study within the last 90 days.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Taking Macitentan Group	Macitentan 10 mg tablet, once daily.	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 4 in the Coronary Microcirculatory Function Indices Assessed by CFR and IMR	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up	Coronary microcirculatory function indices include Coronary Flow Reserve (CFR) and Index of Microcirculatory Resistance (IMR); 1. Coronary Flow Reserve (CFR): A unitless ratio quantifying maximal coronary blood flow augmentation capacity, measured via thermodilution as the ratio of hyperemic to resting coronary flow. The commonly used cut-off value is 2.0 or 2.5. Increased ratio indicates improved microvascular dilation capacity; 2. Index of Microcirculatory Resistance (IMR): A pressure-derived metric (units: mmHg·s) assessing microvascular resistance using thermodilution, calculated as distal coronary pressure multiplied by mean transit time during maximal hyperemia. The commonly used cut-off value is 25. Decreased value indicates reduced microvascular resistance

Secondary Outcome Measures

Name	Time	Method
Change in Score of the Seattle Angina Questionnaire (SAQ)	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up	The Seattle Angina Questionnaire (SAQ) is a 19-item instrument designed to assess the impact of angina on patients' daily lives across five domains: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. Each item is scored on a 0-100 scale, where higher scores indicate fewer symptoms and better quality of life.
Change in Angina Symptoms Assessed by Angina Diary	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up	The angina diary is a structured log where patients record angina episodes, including their frequency, severity, duration, and possible triggers. Symptom severity is classified using a 4-level grading system similar to the Canadian Cardiovascular Society (CCS) angina.
Change in the Score of 6-minute Walking Distance (6MWD)	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up	The 6MWD test evaluates functional exercise capacity by measuring the total distance a patient can walk on a flat surface in 6 minutes. The test reflects cardiovascular fitness and symptom severity.
Incidence of rehospitalisation for angina or heart failure.	4-week follow-up; 8-week follow-up

Trial Locations

Locations (1)

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China