Efficacy and Mechanisms of Macitentan for Non-Coronary Obstructive Angina (MAC-NOCA)

Angina with non-obstructive coronary arteries (ANOCA) is highly prevalent, impairing quality of life and independently associated with cardiovascular events, yet effective treatments are lacking. The endothelin-1 (ET-1)-endothelin receptor (ETR) system is pivotal in ANOCA pathogenesis. Preclinical studies show that ETR blockade or pericyte-specific knockout of ETA receptor improves coronary microcirculatory function in models of myocardial ischemia-reperfusion and diabetes. Clinical evidence indicates ETR antagonists can enhance microvascular endothelial function and myocardial perfusion in ANOCA patients. However, prior studies diagnosed ANOCA based only on symptoms and angiography without precise microvascular functional assessment. Early ETR antagonists also showed frequent adverse effects (e.g., edema, headache), reducing treatment satisfaction. To address this, the investigators will conduct an open-label, single-center, single-arm trial using invasive coronary microcirculatory function testing to accurately phenotype ANOCA and assess microvascular changes. Patients on standard therapy will receive macitentan-a novel ETR antagonist with improved vasodilatory efficacy and safety-to evaluate its effects on coronary microcirculatory function, angina symptoms, and adverse events. Additionally, the investigators will perform multi-omics profiling (proteomics, transcriptomics, metabolomics) on patient blood samples to identify molecular signatures linked to ANOCA subtypes and treatment response, providing evidence for precision intervention strategies in ANOCA.

Study Overview

• Status: Recruiting
• Conditions: Non-Coronary Obstructive Angina
• Intervention / Treatment: Drug: Macitentan 10 mg tablet, once daily.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

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

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • 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 was confirmed via pressure wire-based thermodilution technique.（Patients were classified into subtypes based on coronary microcirculatory function indices: 1) Type I: CFR ≥ 2.5 and IMR < 25; 2) Type II: CFR ≥ 2.5 and IMR ≥ 25; 3) Type III: CFR < 2.5 and IMR < 25; 4) Type IV: CFR < 2.5 and IMR ≥ 25.）
• Sign a written informed consent form.

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
Changes in coronary microcirculation function parameters assessed by CFR from baseline to week 4	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.	the duration of hospital stay, an expected average of 1 week; 4-week follow-up
Changes in coronary microcirculation function parameters assessed by IMR from baseline to week 4	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 1 week; 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.	Endpoint events before administration of macitentan, 1 week and 4 weeks after administration, and 4 weeks after drug withdrawal.
Re-hospitalization due to angina pectoris or heart failure, myocardial infarction, and cardiac death.		Endpoint events at 1 week and 4 weeks after administration of macitentan, and 4 weeks after drug withdrawal.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	All adverse events such as edema, anemia, headache, dizziness, and hypotension.	Endpoint events at 1 week and 4 weeks after administration of macitentan, and 4 weeks after drug withdrawal.

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Macitentan; Endothelin-receptor antagonists; Non-Coronary Obstructive Angina; Coronary microvscular dysfunction
• Additional Relevant MeSH Terms: Pharmaceutical Preparations; Dosage Forms; Tablets; macitentan
• Other Study ID Numbers: 2025-KY-351

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No