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

NCT06811831 | Recruiting Early Phase 1 DMC

• 1 other identifier: 2024-KY-0501
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Microvascular Angina; Macitentan

Keywords

coronary microvascular angina; angina with non-obstructive coronary arteries; Macitentan; Endothelin-receptor antagonists

Outcome Measures

Primary Outcomes (1)

• 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) 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

  the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up

Secondary Outcomes (4)

• 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

• 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

• 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

• Incidence of rehospitalisation for angina or heart failure.

  4-week follow-up; 8-week follow-up

Other Outcomes (1)

• Safety Outcome

  8-week follow-up

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 CFR\<2.5 and/or IMR\>25 assessed by temperature dilution method.

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, 100000, China

RECRUITING

MeSH Terms

Interventions

macitentan; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Yanxiang Gao, Study Principal Investigator

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, 2025
• First Posted: February 6, 2025
• Study Start: November 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 6, 2025

Record last verified: 2025-01

Locations

CN (1)