REDUCER-I: An Observational Study of the Neovasc Reducer™ System

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to collect long term data of the Neovasc Reducer System in subjects with refractory angina pectoris.

Detailed Description
-----------------
This study is a multicenter, multi-country three-arm prospective and retrospective investigation in up to 400 subjects conducted at a maximum of 40 investigational centers. Arm 1 will include eligible prospective subjects. Arm 2 will include subjects who were previously enrolled and treated with the Reducer during the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) study. Arm 3 will include subjects who received a Reducer under CE Mark (unrelated to the COSIRA study).

Official Title
-----------------
REDUCER-I: An Observational Study of the Neovasc Reducer™ System

Conditions
-----------------
Angina Pectoris, Angina Pectoris, Stable, Chronic Stable Angina

Intervention / Treatment
-----------------
* Device: Neovasc Reducer System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria - ALL Arms: Subject has been informed about the study and provides written informed consent prior to enrollment Subject is willing to comply with specified follow-up evaluations Inclusion Criteria - Arm 1: Symptomatic Coronary Artery Disease (CAD) with chronic refractory angina pectoris despite attempted optimal medical therapy Subject has limited treatment options for revascularization by Coronary Artery Bypass Grafting (CABG) or by Percutaneous Coronary Intervention (PCI) Evidence of reversible myocardial ischemia Left Ventricular ejection fraction (LVEF) greater than or equal to 30% Male or non-pregnant female Inclusion Criteria - Arm 2: Subjects previously implanted in the Reducer (treatment) arm of the COSIRA study Inclusion Criteria - Arm 3: Subjects in whom the Reducer was implanted under CE Mark (unrelated to the COSIRA study), prior to enrollment in the Reducer-I study Exclusion Criteria - Arm 1: Acute coronary syndrome within three months prior to enrollment Recent successful revascularization by PCI or CABG within six months prior to enrollment Recent unsuccessful PCI (no relief from symptoms) within 30 days prior to enrollment Unstable angina (recent onset angina, crescendo angina, or rest angina with electrocardiogram [ECG] changes) during the 30 days prior to enrollment Decompensated congestive heart failure (CHF) or hospitalization due to CHF during the three months prior to enrollment 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 Subject cannot undergo exercise tolerance test Subject cannot undergo 6-minute walk test Severe valvular heart disease Subject with pacemaker electrode in the coronary sinus (CS) Subject with recent placement of a new pacemaker or defibrillator electrode in the right atrium within 3 months prior to enrollment. Subject having undergone tricuspid valve replacement or repair Chronic renal failure (serum creatinine >2 mg/dL), including subjects on chronic hemodialysis Moribund subjects, or subjects with comorbidities limiting life expectancy to less than one year Known severe reaction to required procedural medications Known allergy to stainless steel or nickel Magnetic Resonance Imaging (MRI) planned within 8 weeks after Reducer implantation Currently enrolled in another device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints Angiographic Exclusion: Mean right atrial pressure greater than 15mmHg Subject with anomalous or abnormal CS anatomy (e.g., tortuosity, aberrant branch, persistent left superior vena cava [SVC]) CS diameter at the site of planned Reducer implantation less than 9.5 mm or greater than 13 mm

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1 - Prospective<br>Includes eligible subjects in the prospective arm who undergo baseline testing followed by the Neovasc Reducer System implant procedure | Device: Neovasc Reducer System<br>* An aid in the management of chronic refractory angina pectoris<br>* Other names: Reducer;|
| Arm 2 - COSIRA<br>Includes subjects who were previously enrolled and treated with the Neovasc Reducer System during the COSIRA study and agree to participate in this long term follow up study | Device: Neovasc Reducer System<br>* An aid in the management of chronic refractory angina pectoris<br>* Other names: Reducer;|
| Arm 3 - CE Mark<br>Includes subjects who received a Neovasc Reducer System under CE Mark (unrelated to the COSIRA study), and agree to participate in this long term follow up study Arm 3 has been closed to enrollment-June 2017 | Device: Neovasc Reducer System<br>* An aid in the management of chronic refractory angina pectoris<br>* Other names: Reducer;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Canadian Cardiovascular Society (CCS) Grade | The percentage of subjects who experience improvement in their angina symptoms defined as a reduction in CCS grade, at 6 months as compared to baseline | 6 Months | 
| Rate of Occurrence of Device and/or Procedure Related Peri-Procedural Serious Adverse Events (SAE)s | The rate of occurrence of device and / or procedure-related periprocedural SAEs defined as a composite of death, Myocardial Infarction (MI), cardiac tamponade, clinically-driven re-dilation of a Reducer, life-threatening arrhythmias (Ventricular Tachycardia (VT) or Ventricular Fibrillation (VF)), and respiratory failure through 30 days post-implant | 30 days post implant | 
| Occurrence of Major Adverse Cardiac Events (MACE) | Major Adverse Cardiac Events (MACE): a composite of cardiac death, major stroke, and MI through 30-days post-implant | 30 days post implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Canadian Cardiovascular Society (CCS) Grade | The percentage of subjects who experience improvement in their angina symptoms defined as a reduction in CCS grade at 12 months and annually through 5 years post implant as compared to baseline | 12 months and annually through 5 years | 
| Occurrence of Major Adverse Cardiac Events (MACE) | Major Adverse Cardiac Events (MACE): a composite of cardiac death, major stroke, and MI at 6 months, 12 months and annually through 5 years post implant | 6 months, 12 months, and annually through 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronary Sinus, Reducer, Refractory Angina, Angina Pectoris, Angina Pectoris, Stable, Chronic Stable Angina, Persistent Angina, Neovasc Reducer System, Refractory Angina Pectoris, Coronary Sinus Narrowing, Reversible Ischemic Heart Disease, Chronic Angina, End Stage Angina, Coronary Sinus Reduction, Coronary Sinus Reducer, Chronic Refractory Angina, Chronic Refractory Angina Pectoris