Coronary Sinus Reducer for Treatment of Refractory Angina - COSIRA

Study Overview
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Brief Summary
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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.

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

Conditions
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Refractory Angina

Intervention / Treatment
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* Device: Neovasc Reducer
* Device: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is older than 18 years of age 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 Patient has limited treatment options for revascularization by coronary artery bypass grafting or by percutaneous coronary intervention Evidence of reversible ischemia that is attributable to the left coronary arterial system by Dobutamine Echo Left ventricular ejection fraction greater than 25% Male or non-pregnant female (NB: Females of child bearing potential must have a negative pregnancy test) Patient understands the nature of the procedure and provides written informed consent prior to enrollment Patient is willing to comply with specified follow-up evaluation and can be contacted by telephone Exclusion Criteria: Recent (within three months) acute coronary syndrome Recent (within six months) successful PCI or CABG Unstable angina (recent onset angina, crescendo angina, or rest angina with ECG changes) during the thirty days prior to screening De-compensated congestive heart failure (CHF) or hospitalization due to CHF during the three months prior to screening Life threatening rhythm disorders or any rhythm disorders that would require placement of an internal defibrillator and or pacemaker 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 Patient cannot undergo exercise tolerance test (bicycle) for reasons other than refractory angina Severe valvular heart disease Patient with pacemaker or defibrillator electrode in the right atrium, right ventricle, or coronary sinus Patient having undergone tricuspid valve replacement or repair Chronic renal failure (serum creatinine >2 mg/dL), including patients on chronic hemodialysis Moribund patients, or patients with comorbidities limiting life expectancy to less than one year Contraindication to required study medications that cannot be adequately controlled with pre-medication Known allergy to stainless steel or nickel Contraindication to having an MRI performed (NB: Cardiac MRI subset patients only) 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 Mean right atrial pressure higher than or equal to 15 mmHg 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

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reducer<br>Implant Reducer | Device: Neovasc Reducer<br>* Implantation of the Reducer<br>|
| Sham Comparator: Control<br>No treatment | Device: Control<br>* Control - No device implanted<br>|

What is the study measuring?
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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 |