Efficacy and Mechanisms of Macitentan for Non-Coronary Obstructive Angina

NCT07392281 | Recruiting Early Phase 1 DMC

• 1 other identifier: 2025-KY-351
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Coronary Obstructive Angina

Keywords

Non-Coronary Obstructive Angina; Coronary microvscular dysfunction; Macitentan; Endothelin-receptor antagonists

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Change in Score of the Seattle Angina Questionnaire (SAQ)

  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 Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Endpoint events at 1 week and 4 weeks after administration of macitentan, and 4 weeks after drug withdrawal.

Study Arms (1)

Taking Macitentan Group

EXPERIMENTAL

Drug: Macitentan 10 mg tablet, once daily.

Interventions

Macitentan 10 mg tablet, once daily. DRUG

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

Taking Macitentan Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• China-Japan Friendship Hospital: lead

Study Sites (1)

China-Japan Friendship Hospital

Beijing, Beijing Municipality, 100029, China

RECRUITING

MeSH Terms

Interventions

macitentan; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Yanxiang Gao

CONTACT

+86 13811020048; gaoyx1980@163.com

Jingang Zheng

CONTACT

+86-10-84205762; mdjingangzheng@yeah.net

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Cardiology, China-Japan Friendship Hospital

Study Record Dates

• First Submitted: January 22, 2026
• First Posted: February 6, 2026
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: February 6, 2026

Record last verified: 2025-12

Locations

CN (1)