Coronary Sinus Reducer for Treatment of Refractory Angina - COSIRA (COSIRA)

Study to Confirm the Safety and Efficacy of the Reducer on Patients With Refractory Angina

The purpose of this study is to determine if the Reducer is safe and effective in treating the symptoms of refractory angina in patients that suffer from refractory angina who demonstrate reversible ischemia.

Study Overview

• Status: Completed
• Conditions: Refractory Angina
• Intervention / Treatment: Device: Neovasc Reducer; Device: Control

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2020
    • ZNA Middelheim Hospital
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Ottawa Heart Institute
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Rigshospitalet
• Netherlands
  • Utrecht, Netherlands, 3584
    • UMC Utrecht
• Sweden
  • Kristianstad, Sweden, 85
    • Central Hospital Kristianstad
• United Kingdom
  • Bradford, United Kingdom
    • Royal Infirmary of Bradford
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • London, United Kingdom, SE5 9RS
    • King College Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patient is older than 18 years of age
2. Symptomatic CAD with chronic refractory angina pectoris classified as Canadian Cardiovascular Society grade III or IV despite attempted optimal medical therapy for thirty days prior to screening
3. Patient has limited treatment options for revascularization by coronary artery bypass grafting or by percutaneous coronary intervention
4. Evidence of reversible ischemia that is attributable to the left coronary arterial system by Dobutamine Echo
5. Left ventricular ejection fraction greater than 25%
6. Male or non-pregnant female (NB: Females of child bearing potential must have a negative pregnancy test)
7. Patient understands the nature of the procedure and provides written informed consent prior to enrollment
8. Patient is willing to comply with specified follow-up evaluation and can be contacted by telephone

Exclusion Criteria:

1. Recent (within three months) acute coronary syndrome
2. Recent (within six months) successful PCI or CABG
3. Unstable angina (recent onset angina, crescendo angina, or rest angina with ECG changes) during the thirty days prior to screening
4. De-compensated congestive heart failure (CHF) or hospitalization due to CHF during the three months prior to screening
5. Life threatening rhythm disorders or any rhythm disorders that would require placement of an internal defibrillator and or pacemaker
6. Severe chronic obstructive pulmonary disease (COPD) as indicated by a forced expiratory volume in one second that is less than 55% of the predicted value
7. Patient cannot undergo exercise tolerance test (bicycle) for reasons other than refractory angina
8. Severe valvular heart disease
9. Patient with pacemaker or defibrillator electrode in the right atrium, right ventricle, or coronary sinus
10. Patient having undergone tricuspid valve replacement or repair
11. Chronic renal failure (serum creatinine >2 mg/dL), including patients on chronic hemodialysis
12. Moribund patients, or patients with comorbidities limiting life expectancy to less than one year
13. Contraindication to required study medications that cannot be adequately controlled with pre-medication
14. Known allergy to stainless steel or nickel
15. Contraindication to having an MRI performed (NB: Cardiac MRI subset patients only)
16. Currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints
17. Mean right atrial pressure higher than or equal to 15 mmHg
18. Patient with anomalous or abnormal CS as demonstrated by angiogram. Abnormality defined as:

Abnormal CS anatomy (e.g., tortuosity, aberrant branch, persistent left SVC) and/or; CS diameter at the site of planned reducer implantation less than 9.5 mm or greater than 13 mm

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reducer; Implant Reducer	Device: Neovasc Reducer; Implantation of the Reducer
Sham Comparator: Control; No treatment	Device: Control; Control - No device implanted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Canadian Cardiovascular Society Angina Score	A decrease of two or more Canadian Cardiovascular Society Angina Score grades from baseline to six-month post-procedural evaluation in Reducer and Control groups	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success	Successful delivery and deployment of the Reducer to the intended site as assessed by the investigator	24 hours
Procedural success	Technical success and the absence of acute need for clinically-driven intervention to address an Adverse or Serious Adverse Device Effect prior to hospital discharge	24 hours
Periprocedural Serious Adverse Event:	A composite of death, myocardial infarction, cardiac tamponade, clinically-driven re-dilation of a failed Reducer, life-threatening arrhythmia, and respiratory failure through 30 days post-procedure in the Reducer group.	30 days
Periprocedural Serious Adverse Event	A composite of death, myocardial infarction, cardiac tamponade, life-threatening arrhythmia, and respiratory failure through 30 days post-procedure in the control group.	30 days
Major Adverse Events	A composite of cardiac death, major stroke, and myocardial infarction in the Reducer and Control groups through hospital discharge, and at six-month post-procedural evaluations.	6 months
Canadian Cardiovascular Society Angina Score	A decrease one or more Canadian Cardiovascular Society Angina Score grades from baseline to six-month post-procedural evaluation in Reducer and Control groups	6 months
Dobutamine Echo Wall Motion Score Index	Wall motion score index in both the Reducer and control groups at baseline and six-month post-procedural evaluation	6 months
Seattle Angina Questionnaire Score	Seattle Angina Questionnaire in the Reducer and Control groups at baseline and six-month post-procedural evaluation	6 months
Exercise Tolerance Testing	Exercise Tolerance Testing in the Reducer and Control groups at baseline and six-month post-procedural evaluation	6 months

Collaborators and Investigators

• Sponsor: Neovasc Inc.
• Investigators: Principal Investigator: Stefan Verheye, MD, ZNA Middelheim Hospital

Publications and helpful links

General Publications

• Jolicoeur EM, Verheye S, Henry TD, Joseph L, Doucet S, White CJ, Edelman E, Banai S. A novel method to interpret early phase trials shows how the narrowing of the coronary sinus concordantly improves symptoms, functional status and quality of life in refractory angina. Heart. 2021 Jan;107(1):41-46. doi: 10.1136/heartjnl-2020-316644. Epub 2020 Jul 21.
• Verheye S, Jolicoeur EM, Behan MW, Pettersson T, Sainsbury P, Hill J, Vrolix M, Agostoni P, Engstrom T, Labinaz M, de Silva R, Schwartz M, Meyten N, Uren NG, Doucet S, Tanguay JF, Lindsay S, Henry TD, White CJ, Edelman ER, Banai S. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015 Feb 5;372(6):519-27. doi: 10.1056/NEJMoa1402556.
• Jolicoeur EM, Banai S, Henry TD, Schwartz M, Doucet S, White CJ, Edelman E, Verheye S. A phase II, sham-controlled, double-blinded study testing the safety and efficacy of the coronary sinus reducer in patients with refractory angina: study protocol for a randomized controlled trial. Trials. 2013 Feb 15;14:46. doi: 10.1186/1745-6215-14-46.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 13, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Estimate): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 22, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris
• Other Study ID Numbers: #REDCLN-178