Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia and Microvascular Resistance

Study Overview
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Brief Summary
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ORBITA-COSMIC is a randomised, double-blinded, placebo controlled trial of the coronary sinus reducer (CSR). The investigators will compare the effects of CSR versus placebo on myocardial perfusion on MRI, exercise time and symptoms in 50 participants with refractory angina and ischaemia.

Official Title
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Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia and Microvascular Resistance

Conditions
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Refractory Angina

Intervention / Treatment
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* Device: Coronary Sinus Reducer
* Procedure: Placebo Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable coronary artery disease (CAD) not eligible for percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) Evidence of ischaemia on stress perfusion CMR Angina - Canadian Cardiovascular Society Class II-VI on maximal medical therapy Exclusion Criteria: Age<18 years Pregnancy Inability to consent Recent acute coronary syndrome (3 months) Recent revascularisation (6 months) Permanent pacemaker or defibrillator leads in the right heart Severe left ventricular impairment (<25%) Indication for cardiac resynchronisation therapy (CRT) Right atrial pressure ≥15mmHg Life expectancy <1 year Severe renal impairment (eGFR<15) Contraindication to CMR Contraindication to adenosine Ischaemia isolated to inferior wall Ongoing participation in a separate interventional study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CSR<br>Coronary Sinus Reducer implantation | Device: Coronary Sinus Reducer<br>* Coronary Sinus Reducer implantation according to standard clinical protocols<br>* Other names: CSR;|
| Placebo Comparator: Placebo<br>Placebo procedure | Procedure: Placebo Procedure<br>* A placebo procedure involving venous sheath implantation in the right internal jugular vein without proceeding to CSR implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Blood Flow | On cardiac MRI, with adenosine stress, millilitres/gram/minute | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial perfusion reserve (MPR) in ischaemic segments, non ischaemic segments and global MPR | On cardiac MRI | 6 months | 
| Rest myocardial blood flow (MBF) in ischaemic segments, non ischaemic segments and global rest MBF | On cardiac MRI, millilitres/gram/minute | 6 months | 
| Stress myocardial blood flow (MBF) in ischaemic segments, non ischaemic segments and global stress MBF | On cardiac MRI, millilitres/gram/minute | 6 months | 
| MPR in ischaemic segments with inferior and inferoseptal segments excluded | On cardiac MRI | 6 months | 
| MBF in ischaemic segments with inferior and inferoseptal segments excluded | On cardiac MRI, millilitres/gram/minute | 6 months | 
| Endocardial:epicardial ratio of stress MBF | On cardiac MRI | 6 months | 
| Endocardial:epicardial ratio of rest MBF | On cardiac MRI | 6 months | 
| Endocardial:epicardial ratio of MPR | On cardiac MRI | 6 months | 
| Myocardial strain | On cardiac MRI | 6 months | 
| Myocardial scar burden | On cardiac MRI | 6 months | 
| Episodes of angina component of angina symptom score | Daily episodes recorded on ORBITA-COSMIC smartphone application | 6 months | 
| Canadian Cardiovascular Society Class | On a scale from 0-4 with higher scores indicating more severe angina | 6 months | 
| Angina symptom score | Derived from ORBITA-COSMIC smartphone application | 6 months | 
| Seattle Angina Questionnaire (SAQ) Angina Frequency | On a scale from 0-100, with higher scores indicating better outcomes | 6 months | 
| SAQ Angina Physical Limitation | On a scale from 0-100, with higher scores indicating better outcomes | 6 months | 
| SAQ Quality of Life | On a scale from 0-100, with higher scores indicating better outcomes | 6 months | 
| SAQ Treatment Satisfaction | On a scale from 0-100, with higher scores indicating better outcomes | 6 months | 
| SAQ Angina Stability | On a scale from 0-100, with higher scores indicating better outcomes | 6 months | 
| Euro-Qol (EQ-5D-5L) descriptive system | Index derived from 5 question domains, with higher scores indicating better quality of life | 6 months | 
| Euro-Qol (EQ-5D-5L) visual analogue scale | Visual analogue scale from 0-100 with 100 indicating better quality of life | 6 months | 
| Angina related quality of life rated by the MacNew questionnaire | On a scale from 1-7 with higher scores indicating better quality of life | 6 months | 
| Treadmill Exercise Time | Modified Bruce Protocol | 6 months | 
| Absolute coronary flow on pressure/temperature wire assessment | millilitres per minute | 6 months | 
| Absolute coronary resistance on pressure/temperature wire assessment | mmHg/(L/min) | 6 months | 
| Microvascular resistance reserve on pressure/temperature wire assessment |  | 6 months | 
| Coronary flow reserve (CFR) on pressure/temperature wire assessment |  | 6 months | 
| Index of microcirculatory resistance on pressure/temperature wire assessment |  | 6 months | 
| CFR assessed by a pressure and doppler sensor wire |  | 6 months |