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

Imperial College London54 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Interventions

Coronary sinus reducerDEVICE

The Neovasc coronary sinus reducer is an hourglass-shaped stainless steel device inserted percutaneously into the coronary sinus and currently indicated for the treatment of refractory angina.

Sham-procedureOTHER

Implantation procedure with no device implanted

Invasive coronary physiologyDIAGNOSTIC_TEST

Invasive coronary physiology assessment as part of REMEDY-MECH mechanistic substudy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

number of patients consenting to participate in the study.

Consent rate

Time frame: 6 months

Premature withdrawal rate including reasons for withdrawal

Registry of patients either failing screening or unwilling to consent to full trial

Time frame: 6 months

Change in myocardial perfusion

Change at 6 months post randomisation, compared to baseline, in quantitative myocardial perfusion (global myocardial perfusion reserve \[MPR\]) assessed by cardiac MRI.

Time frame: 6 months

Secondary Outcomes

Canadian Cardiovascular Society (CCS) Angina Score

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).

Time frame: 6 months

Seattle Angina Questionnaire (SAQ) score

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.

Time frame: 6 months

Short-form 36 (SF-36)

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.

Time frame: 6 months

Hospital Anxiety and Depression Scale (HADS)

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.

Time frame: 6 months

6-minute walk test (6MWT)

Change in exercise capacity from baseline to 6 months. Distance in metres walked in 6 minutes.

Time frame: 6 months

BORG scale of perceived exertion

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.

Time frame: 6 months

Safety events - rate of major adverse events

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.

Time frame: 6 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts