Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia and Microvascular Resistance (ORBITA-COSMIC)

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Angina
• Intervention / Treatment: Device: Coronary Sinus Reducer; Procedure: Placebo Procedure

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Foley, MBBS MRCP; Phone Number: 020 7594 5735; Email: m.foley@imperial.ac.uk
• Study Contact Backup: Name: Rasha Al-Lamee, PhD MRCP; Phone Number: 020 7594 5735; Email: r.al-lamee13@imperial.ac.uk

Study Locations

• United Kingdom
  • Basildon, United Kingdom
    • Not yet recruiting
    • Basildon and Thurrock Hospitals NHS Foundation Trust
    • Contact: John Davies, PhD; Email: john.davies@btuh.nhs.uk
  • Bournemouth, United Kingdom
    • Not yet recruiting
    • Royal Bournemouth Hospital
    • Contact: Peter O'Kane; Email: peter.o'kane@rbch.nhs.uk
  • London, United Kingdom
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Rasha Al-Lamee, PhD MRCP; Phone Number: 02075945735; Email: rasha.al-lamee@nhs.net
    • Contact: Michael Foley, MBBS MRCP; Phone Number: 02075945735; Email: m.foley@nhs.net
  • London, United Kingdom
    • Not yet recruiting
    • St George's Hospital
    • Contact: James Spratt, MbChB MD; Email: james.spratt@nhs.net
  • London, United Kingdom
    • Not yet recruiting
    • The Royal Brompton Hospital
    • Contact: Jonathan Hill; Email: jmhill@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Medical Research Council; Imperial College Healthcare Nissen Fund

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2021
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: 20HH6457; MR/V001620/1 (Other Grant/Funding Number: Medical Research Council)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No