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

Primary Purpose

Refractory Angina, Microvascular Angina, Microvascular Coronary Artery Disease

Status

Recruiting

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Coronary sinus reducer

Sham-procedure

Invasive coronary physiology

About this trial

This is an interventional treatment trial for Refractory Angina focused on measuring Angina pectoris, Refractory angina, Microvascular angina, Coronary microvascular dysfunction, Coronary sinus reducer, Chest pain, Coronary disease, Myocardial ischaemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age >18 years
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.
Patients willing to consider no change in anti-anginal drug treatment for the duration of their participation in the trial.
Unobstructed coronary arteries with ≤30% epicardial stenoses demonstrated on coronary angiography.
Circumferential subendocardial stress-induced hypoperfusion on CMR (global MPR < 2.5).
Willingness to comply with the specified follow-up evaluation and to be contactable during the period of the trial.
Understands the nature of the trial procedures and provides written informed consent.

Exclusion Criteria:

Epicardial CAD (stenoses > 30%), previous percutaneous coronary intervention (PCI), coronary artery bypass grafting, or myocardial infarction (MI).
Abnormal coronary sinus anatomy (tortuosity, aberrant branch, persistent left superior vena cava)
Coronary sinus diameter at site of implant <9.5mm or >13mm
Mean right atrial pressure <15mmHg at time of implantation
Any structural heart disease including left ventricular hypertrophy; cardiomyopathy; severe valvular heart disease; previous valve replacement; myocardial bridge on angiography; LVEF<45% by CMR.
Clinically or angiographically diagnosed coronary vasospasm
Previous hospitalisation for decompensated heart failure
Pacemaker or defibrillator electrode in the right atrium, right ventricle or coronary sinus
Documented arrhythmia requiring planned implantation of a permanent pacemaker or defibrillator
Chronic kidney disease (creatinine >200 μmol/L; established on renal replacement therapy; functioning renal transplant)
Haemoglobin <80g/L
Contraindications to receiving dual anti-platelet therapy
Severe chronic obstructive pulmonary disease (FEV1 <55% predicted)
Moribund patients with life expectancy < 1year
Known allergy to nickel or steel
Current enrolment in another investigational device or drug trial
Contraindications to CMR or receiving intravenous adenosine
Pregnancy

Sites / Locations

National Heart and Lung Institute (Brompton Campus), Imperial College LondonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

CS Reducer implantation

Sham procedure

Arm Description

Outcomes

Primary Outcome Measures

number of patients consenting to participate in the study.

Consent rate

Premature withdrawal rate including reasons for withdrawal

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

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.

Secondary Outcome Measures

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).

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.

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.

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.

6-minute walk test (6MWT)

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

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.

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.

Full Information

NCT ID

NCT05492110

First Posted

August 4, 2022

Last Updated

July 18, 2023

Sponsor

Imperial College London

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05492110

Brief Title

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

Acronym

REMEDY-PILOT

Official Title

REducing Microvascular Dysfunction in Patients With Angina, Ischaemia and unobstructED coronarY Arteries - a PILOT Study

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 17, 2023 (Actual)

Primary Completion Date

April 6, 2025 (Anticipated)

Study Completion Date

August 7, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Imperial College London

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Randomised, double-blinded, sham-controlled pilot study with parallel arms of participants randomised to CS Reducer or sham procedure

Masking

ParticipantCare ProviderOutcomes 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.

Allocation

Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CS Reducer implantation

Arm Type

Active Comparator

Arm Title

Sham procedure

Arm Type

Sham Comparator

Intervention Type

Device

Intervention Name(s)

Coronary sinus reducer

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Sham-procedure

Intervention Description

Implantation procedure with no device implanted

Intervention Type

Diagnostic Test

Intervention Name(s)

Invasive coronary physiology

Intervention Description

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

Primary Outcome Measure Information:

Title

number of patients consenting to participate in the study.

Description

Consent rate

Time Frame

6 months

Title

Premature withdrawal rate including reasons for withdrawal

Description

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

Time Frame

6 months

Title

Change in myocardial perfusion

Description

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 Outcome Measure Information:

Title

Canadian Cardiovascular Society (CCS) Angina Score

Description

Time Frame

6 months

Title

Seattle Angina Questionnaire (SAQ) score

Description

Time Frame

6 months

Title

Short-form 36 (SF-36)

Description

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

Title

Hospital Anxiety and Depression Scale (HADS)

Description

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

Title

6-minute walk test (6MWT)

Description

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

Time Frame

6 months

Title

BORG scale of perceived exertion

Description

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

Title

Safety events - rate of major adverse events

Description

Time Frame

6 months

Other Pre-specified Outcome Measures:

Title

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

Time Frame

6 months

Title

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.

Time Frame

6 months

Title

Change in global endocardial:epicardial perfusion ratio at rest and after adenosine stress from baseline to 6 months post-randomisation

Time Frame

6 months

Title

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.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >18 years 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. Patients willing to consider no change in anti-anginal drug treatment for the duration of their participation in the trial. Unobstructed coronary arteries with ≤30% epicardial stenoses demonstrated on coronary angiography. Circumferential subendocardial stress-induced hypoperfusion on CMR (global MPR < 2.5). Willingness to comply with the specified follow-up evaluation and to be contactable during the period of the trial. Understands the nature of the trial procedures and provides written informed consent. Exclusion Criteria: Epicardial CAD (stenoses > 30%), previous percutaneous coronary intervention (PCI), coronary artery bypass grafting, or myocardial infarction (MI). Abnormal coronary sinus anatomy (tortuosity, aberrant branch, persistent left superior vena cava) Coronary sinus diameter at site of implant <9.5mm or >13mm Mean right atrial pressure <15mmHg at time of implantation Any structural heart disease including left ventricular hypertrophy; cardiomyopathy; severe valvular heart disease; previous valve replacement; myocardial bridge on angiography; LVEF<45% by CMR. Clinically or angiographically diagnosed coronary vasospasm Previous hospitalisation for decompensated heart failure Pacemaker or defibrillator electrode in the right atrium, right ventricle or coronary sinus Documented arrhythmia requiring planned implantation of a permanent pacemaker or defibrillator Chronic kidney disease (creatinine >200 μmol/L; established on renal replacement therapy; functioning renal transplant) Haemoglobin <80g/L Contraindications to receiving dual anti-platelet therapy Severe chronic obstructive pulmonary disease (FEV1 <55% predicted) Moribund patients with life expectancy < 1year Known allergy to nickel or steel Current enrolment in another investigational device or drug trial Contraindications to CMR or receiving intravenous adenosine Pregnancy

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ranil de Silva, FRCP, PhD

Phone

+44 2073518626

r.desilva@imperial.ac.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Kevin Cheng, BM BCh, MRCP

Phone

+44 2073518626

kevin.cheng@imperial.ac.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ranil E de Silva, FRCP, PhD

Organizational Affiliation

Imperial College London

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Heart and Lung Institute (Brompton Campus), Imperial College London

City

London

ZIP/Postal Code

SW36NP

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ranil de Silva, FRCP, PhD

r.desilva@imperial.ac.uk

First Name & Middle Initial & Last Name & Degree

Kevin Cheng, BM BCh, MRCP

kevin.cheng@imperial.ac.uk

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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