Clinical trial NCT05492110: Coronary Sinus Reducer Implantation in Patients With Ischaemia and Non-obstructed Coronary Arteries and Coronary Microvascular Dysfunction.
Official title: REducing Microvascular Dysfunction in Patients With Angina, Ischaemia and unobstructED coronarY Arteries - a PILOT Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Refractory Angina
Microvascular Angina
Microvascular Coronary Artery Disease
Coronary Disease
Angina Pectoris
Keywords: Angina pectoris
Refractory angina
Microvascular angina
Coronary microvascular dysfunction
Coronary sinus reducer
Chest pain
Coronary disease
Myocardial ischaemia
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Bradford Teaching Hospitals NHS Foundation Trust
name: East and North Hertfordshire NHS Trust
name: Epsom and St Helier University Hospitals NHS Trust
name: Guy's and St Thomas' NHS Foundation Trust
name: Imperial College Healthcare NHS Trust
name: Kingston Hospital NHS Trust
name: London North West Healthcare NHS Trust
name: Oxford University Hospitals NHS Trust
name: Royal Brompton & Harefield NHS Foundation Trust
name: St George's University Hospitals NHS Foundation Trust
name: Liverpool University Hospitals NHS Foundation Trust
First posted: 2022-08-08
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, double-blinded, sham-controlled pilot study with parallel arms of participants randomised to CS Reducer or sham procedure
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: number of patients consenting to participate in the study.
timeFrame: 6 months
measure: Premature withdrawal rate including reasons for withdrawal
timeFrame: 6 months
measure: Change in myocardial perfusion
timeFrame: 6 months
Secondary outcomes:
measure: Canadian Cardiovascular Society (CCS) Angina Score
timeFrame: 6 months
measure: Seattle Angina Questionnaire (SAQ) score
timeFrame: 6 months
measure: Short-form 36 (SF-36)
timeFrame: 6 months
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 6 months
measure: 6-minute walk test (6MWT)
timeFrame: 6 months
measure: BORG scale of perceived exertion
timeFrame: 6 months
measure: Safety events - rate of major adverse events
timeFrame: 6 months
Other outcomes:
measure: Change in absolute global myocardial perfusion (ml/min/g) at rest and during adenosine stress (transmural, endocardial, epicardial) from baseline to 6 months post-randomisation
timeFrame: 6 months
measure: Change in absolute myocardial perfusion (ml/min/g) at rest and during adenosine stress (transmural, endocardial, epicardial) from baseline to 6 months post-randomisation in the distribution territory of the left coronary circulation.
timeFrame: 6 months
measure: Change in global endocardial:epicardial perfusion ratio at rest and after adenosine stress from baseline to 6 months post-randomisation
timeFrame: 6 months
measure: Change in endocardial:epicardial perfusion ratio at rest and after adenosine stress from baseline to 6 months post-randomisation in the distribution territory of the left coronary circulation.
timeFrame: 6 months
Locations:
city: London
country: United Kingdom
facility: National Heart and Lung Institute (Brompton Campus), Imperial College London
Study officials:
affiliation: Imperial College London
name: Ranil E de Silva, FRCP, PhD
role: PRINCIPAL_INVESTIGATOR
References: