Coronary Sinus Reducer Implantation in Patients With Ischaemia and Non-obstructed Coronary Arteries and Coronary Microvascular Dysfunction.

Not Applicable

Recruiting

• Conditions: Refractory Angina; Microvascular Angina; Microvascular Coronary Artery Disease; Angina Pectoris; Coronary Disease
• Interventions: Device: Coronary sinus reducer; Other: Sham-procedure; Diagnostic Test: Invasive coronary physiology

• Registration Number: NCT05492110
• Lead Sponsor: Imperial College London

Brief Summary

To demonstrate the feasibility and efficacy of the CS Reducer for the treatment of patients with ischaemia and non-obstructed coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) and through a nested mechanistic substudy investigate the physiological responses in the coronary microcirculation responsible for changes in myocardial perfusion.

Detailed Description

Symptomatic angina in patients with ischaemia and non-obstructed coronary arteries (INOCA) is common and associated with increased morbidity and adverse outcomes. Myocardial ischaemia often arises from coronary microvascular dysfunction (CMD). Current treatments are limited, and novel evidence-based therapies are needed to address this large unmet clinical need. The Coronary Sinus Reducer (CS Reducer) is a new treatment for refractory angina, which creates a focal narrowing in the coronary sinus that increases back pressure and redistributes blood into ischaemic myocardium at the level of the microcirculation. However the precise mechanism remains unknown. This study will be a randomised double-blinded sham-controlled pilot study (REMEDY-PILOT) to confirm acceptability of CS Reducer implantation, demonstrate feasibility to recruit and quantify its effect on myocardial perfusion. A nested mechanistic substudy within REMEDY-PILOT will test the hypothesis that CS Reducer implantation alters measures of invasive coronary microcirculatory physiology as the mechanistic basis for observed changes in quantitative CMR stress perfusion, symptoms and quality of life.

Study Timeline

• Study First Submitted: 2022-08-04
• Study First Submitted QC: 2022-08-05
• Study First Posted: 2022-08-08
• Study Start: 2023-04-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-03
• Primary Completion: 2026-03-06
• Study Completion: 2026-03-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

1. Age >18 years
2. Ongoing symptomatic angina, CCS Class II-IV, for ≥3 months despite background treatment with at least two anti-anginal drug at the maximal tolerated dose.
3. Patients willing to consider no change in anti-anginal drug treatment for the duration of their participation in the trial.
4. Unobstructed coronary arteries with ≤50% epicardial stenoses demonstrated on coronary angiography.
5. Stress-induced hypoperfusion on CMR (Global MPR ≤ 2.2).
6. Willingness to comply with the specified follow-up evaluation and to be contactable during the period of the trial.
7. Understands the nature of the trial procedures and provides written informed consent.

Exclusion Criteria

1. Epicardial CAD in a main coronary artery (stenoses >50%, RFR≤0.92 or FFR≤0.80), coronary artery bypass grafting, or myocardial infarction (MI).
2. Previous PCI within 6 months
3. PCI with stent insertion for acute MI or chronic total occlusion (CTO)
4. Abnormal coronary sinus anatomy (tortuosity, aberrant branch, persistent left superior vena cava)
5. Coronary sinus diameter at site of implant <9.5mm or >13mm
6. Mean right atrial pressure <15mmHg at time of implantation
7. Any structural heart disease including left ventricular hypertrophy; cardiomyopathy; severe valvular heart disease; previous valve replacement; myocardial bridge on angiography; LVEF<45% by CMR.
8. Clinically or angiographically diagnosed coronary vasospasm
9. Previous hospitalisation for decompensated heart failure
10. Pacemaker or defibrillator electrode in the right atrium, right ventricle or coronary sinus
11. Documented arrhythmia requiring planned implantation of a permanent pacemaker or defibrillator
12. Chronic kidney disease (creatinine >200 micromol/L; established on renal replacement therapy; functioning renal transplant)
13. Haemoglobin <80g/L
14. Contraindications to receiving dual antiplatelet therapy
15. Severe chronic obstructive pulmonary disease (FEV1 <55% predicted)
16. Moribund patients with life expectancy < 1year
17. Known allergy to nickel or steel
18. Current enrolment in another investigational device or drug trial
19. Contraindications to CMR or receiving intravenous adenosine
20. Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CS Reducer implantation	Coronary sinus reducer	-
CS Reducer implantation	Invasive coronary physiology	-
Sham procedure	Sham-procedure	-
Sham procedure	Invasive coronary physiology	-

Primary Outcome Measures

Name	Time	Method
Premature withdrawal rate including reasons for withdrawal	6 months	Registry of patients either failing screening or unwilling to consent to full trial
Change in myocardial perfusion	6 months	Change at 6 months post randomisation, compared to baseline, in quantitative myocardial perfusion (global myocardial perfusion reserve \[MPR\]) assessed by cardiac MRI.
number of patients consenting to participate in the study.	6 months	Consent rate

Secondary Outcome Measures

Name	Time	Method
Short-form 36 (SF-36)	6 months	Change in SF-36 scores from baseline to 6 months. Validated questionnaire to assess quality of life. 36 items each scored from 0-100 with higher scores indicating a more favourable health state.
Hospital Anxiety and Depression Scale (HADS)	6 months	Change in HADS score from baseline to 6 months. Scores range from 0 to 21. Normal results are indicated by lower scores. Validated questionnaire to assess psychological wellbeing.
Safety events - rate of major adverse events	6 months	The rate of occurrence of a composite of death, myocardial infarction (MI), pericardial effusion requiring surgical or percutaneous intervention, device embolisation, or BARC 3 or 5 bleeding evaluation in the CS Reducer arm compared to the sham-procedure arm.
Canadian Cardiovascular Society (CCS) Angina Score	6 months	Change in CCS class from baseline to 6 months post-randomisation. The CCS grading system for angina is a clinical tool used by doctors to assess the degree of severity of a patient's angina. Possible scores range from Class 0 (asymptomatic angina) to Class IV (angina at rest).
BORG scale of perceived exertion	6 months	Change in BORG scale from baseline to 6 months. Scores range from 0 to 20 (BORG scale) or 0 to 10 (Modified BORG scale). The higher the self-reported score, the greater perceived exertion.
6-minute walk test (6MWT)	6 months	Change in exercise capacity from baseline to 6 months. Distance in metres walked in 6 minutes.
Seattle Angina Questionnaire (SAQ) score	6 months	Change in SAQ score from baseline to 6 months. The Seattle Angina Questionnaire (SAQ) is a disease-specific questionnaire used to quantify patients' symptoms of angina and the extent to which their angina affects their functioning and quality of life. Possible scores range from 0 (daily angina) to 100 (no angina). Lower scores indicate worse angina symptoms.

Trial Locations

Locations (1)

National Heart and Lung Institute (Brompton Campus), Imperial College London; 🇬🇧 London, United Kingdom