Clinical trial NCT06811831: Evaluation of the Efficacy of MACitentan in the Treatment of CoronaryMICrovascular Angina (MACMIC)
Official title: Evaluation of the Efficacy of MACitentan in the Treatment of CoronaryMICrovascular Angina: a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Coronary Microvascular Angina
Macitentan
Keywords: coronary microvascular angina
angina with non-obstructive coronary arteries
Macitentan
Endothelin-receptor antagonists
Lead sponsor: China-Japan Friendship Hospital
Sponsor class: OTHER
First posted: 2025-02-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Week 4 in the Coronary Microcirculatory Function Indices Assessed by CFR and IMR
timeFrame: the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up
Secondary outcomes:
measure: Change in Score of the Seattle Angina Questionnaire (SAQ)
timeFrame: the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up
measure: Change in Angina Symptoms Assessed by Angina Diary
timeFrame: the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up
measure: Change in the Score of 6-minute Walking Distance (6MWD)
timeFrame: the duration of hospital stay, an expected average of 2 weeks; 4-week follow-up; 8-week follow-up
measure: Incidence of rehospitalisation for angina or heart failure.
timeFrame: 4-week follow-up; 8-week follow-up
Other outcomes:
measure: Safety Outcome
timeFrame: 8-week follow-up
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
Study officials:
References: