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

Evaluation of the Efficacy of MACitentan in the Treatment of CoronaryMICrovascular Angina: a Pilot Study

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Microvascular Angina; Macitentan
• Intervention / Treatment: Drug: Macitentan 10 mg tablet, once daily.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yanxiang Gao, Study Principal Investigator; Phone Number: +86 13811020048; Email: gaoyx1980@163.com
• Study Contact Backup: Name: Jingang Zheng; Phone Number: +86-10-84205762; Email: mdjingangzheng@yeah.net

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • China-Japan Friendship Hospital
      • Contact: Jingang Zheng; Phone Number: +86-10-84205762; Email: mdjingangzheng@yeah.net

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Taking Macitentan Group	Drug: Macitentan 10 mg tablet, once daily.; After the patient signed an informed consent form, Macitentan was given as an oral medication (10 mg once daily) for a period of 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 4 in the Coronary Microcirculatory Function Indices Assessed by CFR and IMR	Coronary microcirculatory function indices include Coronary Flow Reserve (CFR) and Index of Microcirculatory Resistance (IMR); 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; 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	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Score of the Seattle Angina Questionnaire (SAQ)	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.	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up
Change in Angina Symptoms Assessed by Angina Diary	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.	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up
Change in the Score of 6-minute Walking Distance (6MWD)	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.	the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up
Incidence of rehospitalisation for angina or heart failure.		4-week follow-up; 8-week follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome	Occurrence of all adverse events such as hydrosodium storage, anaemia, headache and hypotension et al.	8-week follow-up

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: February 1, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Macitentan; coronary microvascular angina; angina with non-obstructive coronary arteries; Endothelin-receptor antagonists
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Chest Pain; Angina Pectoris; Microvascular Angina; Molecular Mechanisms of Pharmacological Action; Endothelin A Receptor Antagonists; Endothelin Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: 2024-KY-0501

Drug and device information, study documents

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