Coronary Sinus Reducer in Coronary Microvascular Disease (REDUCE CMD)

Impact of the Coronary Sinus Reducer on Coronary Flow Reserve and Symptoms in Patients With Coronary Microvascular Disease

Coronary microvascular dysfunction (CMD) is a common cause of treatment- resistant angina that lacks evidence-based treatment options. The coronary sinus reducer (CSR) is an hourglass-shaped stainless steel mesh, designed to create a controlled narrowing of the coronary sinus (CS). By augmenting CS pressure, CSR implantation was shown to improve myocardial perfusion, potentially providing a novel treatment for patients with CMD. REDUCE CMD is a placebo-controlled study of CSR in 50 patients with CMD. The main study endpoints are the change in coronary flow reserve from baseline to 6 months in the CSR-arm versus the placebo arm, and the difference in number of daily episodes of angina recorded on the ORBITA-app at 6 month follow-up in the CSR-arm versus the placebo arm.

Study Overview

• Status: Enrolling by invitation
• Conditions: Coronary Microvascular Disease; Angina (Stable)
• Intervention / Treatment: Other: Sham CSR procedure; Device: Coronary sinus reducer

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Maasstad Ziekenhuis
  • Utrecht, Netherlands, 3584CX
    • UMC Utrecht

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

1. Coronary microvascular dysfunction in the left anterior descending coronary artery (LAD) as expressed by abnormal absolute coronary flow reserve (CFR<2.5) confirmed during the index study procedure using the continuous thermodilution technique and saline-induced coronary hyperaemia.
2. Angina - Canadian Cardiovascular Society Class II-IV on at least two anti-anginals or maximally tolerated medical therapy if less than two.
3. Patient understands the nature of the procedure and provides written informed consent for the study prior to enrolment.

Exclusion criteria

1. Age < 18 years.
2. Absence of symptoms reported on the ORBITA-app during the 2-week screening period.
3. Presence of hemodynamically significant epicardial stenoses based on both non- hyperaemic pressure ratio (NHPR; iFR≤0.89, or RFR≤0.89, or dFR/dPR≤0.89) or fractional flow reserve (FFR≤0.80) assessments.
4. Prior positive acetylcholine provocation test with respect to epicardial vasospasm following the COVADIS criteria.
5. Mean right atrial pressure ≥15 mmHg
6. Severe pulmonary hypertension.
7. Coronary sinus anatomy not suitable for CSR implantation.
8. Pregnancy or planned pregnancy within the next 12 months.
9. Recent acute coronary syndrome (within 3 months).
10. Recent revascularization with PCI (within 6 months).
11. Severe arrhythmias, including chronic atrial fibrillation with persistent rapid ventricular response (>100bpm despite medication).
12. Indication for cardiac resynchronization therapy.
13. Severe left ventricular impairment (left ventricular ejection fraction <35%).
14. NYHA class IV or decompensated heart failure or hospitalization due to heart failure within 90 days before the index procedure.
15. Recent implantation of a permanent pacemaker or defibrillator lead in the right ventricle or atrium (within 90 days before the index procedure).
16. Presence of a pacemaker lead in the coronary sinus.
17. Severe valvular heart disease.
18. History of tricuspid valve replacement or repair.
19. Contra-indication to short term dual antiplatelet therapy or lifelong aspirin treatment.
20. Currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints.
21. Known inability to tolerate contrast medium.
22. Life expectancy <1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham; Patients in this arm undergo a sham CSR procedure.	Other: Sham CSR procedure; Patients will undergo a complete sham CSR implantation procedure without actual deployment of the CSR.; Other Names: Sham
Experimental: CSR arm; Patients in this arm undergo coronary sinus reducer implantation.	Device: Coronary sinus reducer; Implantation of a Coronary Sinus Reducer device; Other Names: reducer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coronary flow reserve	Change in coronary flow reserve from baseline to 6 months in the CSR-arm versus the placebo arm (measured by the continuous flow thermodilution technique using saline-induced coronary hyperaemia).	6 months
Angina episodes	Difference in number of daily episodes of angina recorded on the ORBITA-app at 6 month follow-up in the CSR-arm versus the placebo arm.	6 months

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Radboud University Medical Center; Maasstad Hospital, Rotterdam; VieCuri, Venlo, the Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: January 4, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Angina; Coronary sinus reducer; Coronary microvascular disease
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Chest Pain; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Angina Pectoris; Angina, Stable; Microvascular Angina; salicylhydroxamic acid
• Other Study ID Numbers: REDUCE CMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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