Refractory Angina, Microvascular Angina, Microvascular Coronary Artery Disease, Coronary Disease, Angina Pectoris, INOCA (Ischemia With Non Obstructive Coronary Artery Disease), ANOCA - Angina With Non-obstructive Coronary Arteries, Coronary Microvascular Dysfunction (CMD)
Conditions
Keywords
Angina pectoris, Refractory angina, Microvascular angina, Coronary microvascular dysfunction, Coronary sinus reducer, Chest pain, Coronary disease, Myocardial ischaemia, INOCA (ischemia with non obstructive coronary artery disease), ANOCA - angina with non-obstructive coronary arteries
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.
Interventions
DEVICECoronary sinus reducer
The Shockwave Reducer is an hourglass-shaped stainless steel device inserted percutaneously into the coronary sinus and currently indicated for the treatment of refractory angina.
OTHERSham Procedure
Implantation procedure with no device implanted
DIAGNOSTIC_TESTInvasive coronary physiology
Invasive coronary physiology assessment as part of REMEDY-MECH mechanistic substudy
Sponsors
Imperial College London
Bradford Teaching Hospitals NHS Foundation Trust
East and North Hertfordshire NHS Trust
Epsom and St Helier University Hospitals NHS Trust
Guy's and St Thomas' NHS Foundation Trust
Imperial College Healthcare NHS Trust
Kingston Hospital NHS Trust
London North West Healthcare NHS Trust
Oxford University Hospitals NHS Trust
Royal Brompton & Harefield NHS Foundation Trust
St George's University Hospitals NHS Foundation Trust
Liverpool University Hospitals NHS Foundation Trust
East Kent Hospitals University NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants will be randomised and blinded to CS Reducer of sham procedure. All follow-up assessments will be performed by a blinded parallel team to ensure blinded outcomes analysis.
Intervention model description
Randomised, double-blinded, sham-controlled pilot study with parallel arms of participants randomised to CS Reducer or sham procedure
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 drugs 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), percutaneous coronary intervention (PCI; within previous 6 months, stent insertion for acute Type 1 MI or chronic total occlusion (CTO)), coronary artery bypass grafting, or confirmed Type 1 myocardial infarction (MI). 2. Abnormal coronary sinus anatomy (tortuosity, aberrant branch, persistent left superior vena cava) 3. Coronary sinus diameter unsuitable for device implantation at operator discretion 4. Mean right atrial pressure \>15mmHg at time of implantation 5. Structural heart disease including left ventricular hypertrophy with raised LV mass index; cardiomyopathy; severe valvular heart disease; previous valve replacement; significant myocardial bridge on angiography; LVEF\<45% by CMR. 6. Clinically or angiographically diagnosed coronary vasospasm 7. Previous hospitalisation for decompensated heart failure 8. Pacemaker or defibrillator electrode in the right atrium, right ventricle or coronary sinus 9. Documented arrhythmia requiring planned implantation of a permanent pacemaker or defibrillator 10. Chronic kidney disease (creatinine \>200 micromol/L; established on renal replacement therapy; functioning renal transplant) 11. Haemoglobin \<80g/L 12. Contraindications to receiving dual antiplatelet therapy 13. Severe chronic obstructive pulmonary disease (FEV1 \<55% predicted) 14. Moribund patients with life expectancy \< 1year 15. Known allergy to nickel or steel 16. Current enrolment in another investigational device or drug trial 17. Contraindications to CMR or receiving intravenous adenosine 18. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients consenting to participate in the study | 6 months | Consent rate |
| 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 in segmental endocardial myocardial perfusion reserve (MPR) \[ratio of absolute MBF after adenosine stress to rest MBF corrected for rate-pressure product\] at 6-months follow-up after CS Reducer compared to a sham procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORBITA smartphone application | 6 months | Daily angina episodes |
| 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. |
| 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. |
| EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) | 6 months | Change in EQ-5D-5L index score from baseline to 6 months. Quality of life assessed using the EQ-5D-5L, a five-domain descriptive system generating an index score from 0 (worst health) to 1 (best health), with higher scores indicating better quality of life. |
| 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). |
| 6-minute walk test (6MWT) | 6 months | Change in exercise capacity from baseline to 6 months. Distance in metres walked in 6 minutes. |
| 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. |
| Safety events | 6 months | Serious adverse events resulting from the CS Reducer procedure |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORRanil E de Silva, FRCP, PhD
Imperial College London
Outcome results
None listed