title: 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.
abstract: BACKGROUND
  A growing population of patients lives with severe coronary artery disease not amenable to coronary revascularization and with refractory angina despite optimal medical therapy. Percutaneous reduction of the coronary sinus is an emerging treatment for myocardial ischemia that increases coronary sinus pressure to promote a transcollateral redistribution of coronary artery in-flow from nonischemic to ischemic subendocardial territories. A first-in-man study has demonstrated that the percutaneous reduction of the coronary sinus can be performed safely in such patients. The COSIRA trial seeks to assess whether a percutaneous reduction of the coronary sinus can improve the symptoms of refractory angina in patients with limited revascularization options.
  
  
  METHODS
  The COSIRA trial is a phase II double-blind, sham-controlled, randomized parallel trial comparing the percutaneously implanted coronary sinus Reducer (Neovasc Inc, Richmond, BC, Canada) to a sham implantation in 124 patients enrolled in Canada, Belgium, England, Scotland, Sweden and Denmark. All patients need to have stable Canadian Cardiovascular Society (CCS) class III or IV angina despite optimal medical therapy, with evidence of reversible ischemia related to disease in the left coronary artery, and a left ventricular ejection fraction >25%. Participants experiencing an improvement in their angina ≥2 CCS classes six months after the randomization will meet the primary efficacy endpoint. The secondary objective of this trial is to test whether coronary sinus Reducer implantation will improve left ventricular ischemia, as measured by the improvement in dobutamine echocardiogram wall motion score index and in time to 1 mm ST-segment depression from baseline to six-month post-implantation.
  
  
  CONCLUSIONS
  Based on previous observations, the COSIRA is expected to provide a significant positive result or an informative null result upon which rational development decisions can be based. Patient safety is a central concern and extensive monitoring should allow an appropriate investigation of the safety related to the coronary sinus Reducer.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier - NCT01205893.
authors: Montreal Heart Institute, Université de Montréal, 5000 Bélanger Street East, Montréal, Québec Q H1T 1C8, Canada. marc.jolicoeur@icm-mhi.org
authors: E Marc
authors: EM
authors: Jolicœur
authors: Shmuel
authors: S
authors: Banai
authors: Timothy D
authors: TD
authors: Henry
authors: Marc
authors: M
authors: Schwartz
authors: Serge
authors: S
authors: Doucet
authors: Christopher J
authors: CJ
authors: White
authors: Elazer
authors: E
authors: Edelman
authors: Stefan
authors: S
authors: Verheye
mesh_terms: D060050:Angina, Stable / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D002170:Canada; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000295:instrumentation*; D062906:Cardiac Catheters; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002985:Clinical Protocols; D017023:Coronary Angiography; D003326:Coronary Circulation; D054326:Coronary Sinus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004311:Double-Blind Method; D004351:Drug Resistance; D025401:Echocardiography, Stress; D004867:Equipment Design; D005060:Europe; D006801:Humans; D055414:Myocardial Perfusion Imaging / Q000379:methods; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012107:Research Design; D013318:Stroke Volume; D011795:Surveys and Questionnaires; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D002317:Cardiovascular Agents