COSIRA-II: Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II
Study Details
Study Description
Brief Summary
To demonstrate the safety and effectiveness of the Reducer system for treatment of patients with refractory angina pectoris treated with maximally tolerated guideline-directed medical therapy who demonstrate objective evidence of reversible myocardial ischemia in the distribution of the left coronary artery and who are deemed unsuitable for revascularization.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The COSIRA-II study is a multicenter, randomized (1:1 ratio), double-blinded, sham-controlled clinical trial.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1 (treatment arm):Implantation of the Reducer device
|
Device: Arm 1: treatment with Neovasc Reducer
Neovasc reducer is an implantable device being evaluated for the alleviation of refractory angina symptoms
|
| Sham Comparator: Arm 2 (sham-control arm): Control (no device implantation)
|
Other: Arm 2 (control): Implantation procedure with no device implanted
No device is implanted
|
Outcome Measures
Primary Outcome Measures
- Effectiveness [6 months]
Change in total exercise duration in a modified Bruce treadmill exercise tolerance testing evaluation in the Treatment arm compared to Sham-control arm.
- Safety Events [6 months]
The rate of occurrence of a composite of death, myocardial infarction (MI), pericardial effusion requiring surgical or percutaneous intervention, device embolization, or BARC 3 or 5 bleeding evaluation in the Treatment arm compared to the Sham-control arm.
Secondary Outcome Measures
- Canadian Cardiovascular Society (CCS) Angina Score [6 months]
Improvement by greater than or equal to 1 CCS angina grade. 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).
- Canadian Cardiovascular Society (CCS) Angina Score [6 months]
Improvement by greater than or equal to 2 CCS angina grades. 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 [6 months]
Change in Angina Stability domain score from the Seattle Angina Questionnaire (SAQ). 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.
Other Outcome Measures
- Canadian Cardiovascular Society (CCS) Angina Score [12 months, 2 years, 3 years, 4 years, and 5 years]
Improvement by greater than or equal to 1 and greater than or equal to 2 CCS angina grades compared to baseline. 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).
- Angina Burden [6 and 12 months]
Angina frequency and burden compared to baseline
- Activity [6 and 12 months]
Measure of activity assessed by actigraphy compared to baseline
- Exercise Tolerance Testing [6 and 12 months]
Change in ETT parameters compared to baseline
- Exercise Tolerance Testing [12 months]
Change in total exercise duration compared to baseline
- Doctor Visits [6 months, 12 months, 2 years, 3 years, 4 years, and 5 years]
Number of unplanned office visits due for angina, and any hospitalizations or emergency department visits compared to baseline
- Exercise Tolerance Testing [6 and 12 months]
Total exercise duration
- Seattle Angina Questionnaire (SAQ) Score [6 month, 12 month, 2 years, 3 years, 4 years, and 5 years]
Change in other Seattle Angina Questionnaire (SAQ) domain scores compared to baseline. 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.
- Adverse Events [30 day, 6 month, 12 month, 2 years, 3 years, 4 years, and 5 years]
Number of deaths, myocardial infarctions, strokes, unplanned revascularization procedures in-hospital, at 30 days, 3 months, 6 months, 12 months and annually post procedure (all and ischemia-relate) and composite major adverse cardiac events (cardiac death, myocardial infarction, stroke, or unplanned revascularization for ischemia) in-hospital
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject is older than 18 years of age
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Symptomatic coronary artery disease (CAD) with greater than or equal to 90 days of persistent refractory angina pectoris classified as CCS Grade III or IV despite maximally tolerated guideline directed medical therapy
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Must have attempted treatment with the maximally tolerated dose of at least three of the four (and preferably all four) approved classes of anti-anginal agents: long-acting nitrates, calcium channel blockers (either a dihydropyridine or a non-dihydropyridine), beta blockers, and ranolazine. The regimen must be stable for greater than 2 months prior to enrollment, with no intent to change the medical regimen for at least 12 months after randomization
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Subject has either no treatment options for revascularization by coronary artery bypass grafting or by percutaneous coronary intervention, or is otherwise unsuitable or high risk for revascularization
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Evidence of either exercise or pharmacologically induced reversible ischemia severity by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFRCT, FFR, iFR, or other non-hyperemic FDA approved tests in the distribution of the left coronary artery (LCA). Note: if the subject has evidence of ischemia in both the LCA and RCA distributions, the extent of ischemia must be greater in the LCA distribution
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Functional limitation due to refractory angina as defined by a modified Bruce exercise tolerance test duration of greater than or equal to 2 minutes but less than or equal to 8 minutes
- Subject has ETT variability less than 20% between last two ETTs performed
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Left ventricular ejection fraction (LVEF) greater than or equal to 30% within the 12-months prior to procedure (must be reassessed after any intervening myocardial infarction); the most recent LVEF assessment is used as the qualifying test
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Subject is willing and able to sign informed consent
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Subject is willing to comply with the specified follow-up evaluations
Exclusion Criteria:
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Recent (within 30 days prior to enrollment) troponin or CKMB positive acute coronary syndrome (NSTEMI or STEMI).
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Recent successful revascularization by CABG or PCI within six months prior to enrollment
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Recent unsuccessful PCI (e.g., no relief from symptoms, failed attempt to open a chronic total occlusion) within 30 days prior to enrollment
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The predominant manifestation of angina is dyspnea
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Has extra-coronary contributory causes of angina - e.g., untreated hyperthyroidism, anemia (hgb <10 g/dL), uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg despite medications), atrial fibrillation with rapid ventricular response (consistently >100 bpm despite medications) or other tachyarrhythmia, severe aortic stenosis, hypertrophic cardiomyopathy with left ventricular outflow tract obstruction or asymmetric septal hypertrophy (concentric left ventricular hypertrophy is not an exclusion criterion), etc.
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NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF during the 90 days prior to enrollment
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Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker
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Severe chronic obstructive pulmonary disease (COPD) as indicated by a forced expiratory volume in one second (FEV1) that is less than 55% of the predicted value, or need for home daytime oxygen or oral steroids
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Severe valvular heart disease (any valve)
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Moderate or severe RV dysfunction by echocardiography
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Pacemaker electrode/lead is present in the coronary sinus
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A Class I indication is present for an implantable defibrillator or cardiac resynchronization therapy according to ACCF/AHA/HRS guidelines
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Recent implantation of a new pacemaker or defibrillator lead with electrode in the right atrium within 90 days of enrollment
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Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD formula) or subjects on chronic dialysis
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Known allergy to stainless steel or nickel
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Any clinical condition that might interfere with the trial protocol or the subject's ability to be compliant with the trial protocol (e.g., active alcohol or drug abuse, dementia, magnetic resonances imaging (MRI) planned within 8 weeks of randomization, etc.)
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Currently enrolled in another investigational device or drug trial that has not reached its primary endpoint or that might clinically interfere with the current trial endpoints or procedures
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Pregnant or planning pregnancy within the next 12 months (women of reproductive potential must have a negative pregnancy test within 7 days of the randomization procedure)
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Subject is part of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.
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Inability to tolerate dual antiplatelet therapy for 6 months if not on a chronic oral anticoagulant, or inability to tolerate a P2Y12 inhibitor for at least 6 months if on a chronic oral anticoagulant
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Comorbidities limiting life expectancy to less than one year
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Cardiac and Vascular Institute | Gainesville | Florida | United States | 32605 |
| 2 | Cardiovascular Research Institute of Kansas | Wichita | Kansas | United States | 67226 |
| 3 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02120 |
| 4 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 5 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 6 | Mount Sinai Medical Center | New York | New York | United States | 10003 |
| 7 | Columbia University Medical Center/NYPH | New York | New York | United States | 10032 |
| 8 | St. Francis Hospital | Roslyn | New York | United States | 11576 |
| 9 | The Christ Hospital | Cincinnati | Ohio | United States | 45219 |
| 10 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 11 | TriStar Centennial Medical Center | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Neovasc Inc.
Investigators
- Principal Investigator: Timothy D Henry, MD, The Christ Hospital Health Network
- Principal Investigator: Gregg W Stone, MD, Mt. Sinai Heart Health
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 022-REDUCLN-002