Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II (COSIRA-II)

April 20, 2026 updated by: Shockwave Medical, Inc.
To demonstrate the safety and effectiveness of the Shockwave Reducer 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. A non-randomized single-arm registry will further assess the safety and effectiveness of the Shockwave Reducer in selected subjects with reversible myocardial ischemia in the distribution of the right coronary artery and who are deemed unsuitable for revascularization, subjects without documented obstructive coronary disease and abnormal coronary flow reserve (ANOCA), and subjects who cannot complete an exercise tolerance test due to lower limb amputation (above the ankle) or other physiologic condition with documented chronic mobility or balance issues that require the use of a walking aid.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The COSIRA-II study is a multicenter, randomized (1:1 ratio), double-blinded, sham-controlled clinical trial.

Study Type

Interventional

Enrollment (Estimated)

380

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V521M9
        • Recruiting
        • Vancouver General Hospital
        • Contact:
        • Principal Investigator:
          • David Wood
    • Ontario
      • Ottawa, Ontario, Canada, K1Y4W7
        • Recruiting
        • University of Ottawa Heart Institute
        • Contact:
        • Principal Investigator:
          • Mariano Labinaz
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • Toronto General Hospital (UHN)
        • Contact:
        • Principal Investigator:
          • Vladimir Dzavik
    • Quebec
      • Montreal, Quebec, Canada, H2X 0C1
      • Québec, Quebec, Canada, G1V4G5
        • Recruiting
        • IUCPQ-Ulaval
        • Contact:
        • Principal Investigator:
          • Jean-Michael Paradis, MD
  • United Kingdom
      • Basildon, United Kingdom, SS16 5NL
        • Recruiting
        • Essex Cardiothoracic Centre
        • Contact:
        • Principal Investigator:
          • Thomas Keeble, MD
      • Birmingham, United Kingdom, B15 2GW
        • Recruiting
        • Queen Elizabeth Hospital Birmingham
        • Contact:
        • Principal Investigator:
          • Alex Zaphiriou, MD
      • Bristol, United Kingdom, BS2 8HW
        • Recruiting
        • Bristol Heart Institute
        • Contact:
        • Principal Investigator:
          • Ioannis Felekos, MD
      • Cambridge, United Kingdom, |CB2 0AY
        • Recruiting
        • Royal Papworth Hospital
        • Contact:
        • Principal Investigator:
          • Stephen Hoole, MD
      • Dorchester, United Kingdom, DT1 2JY
        • Recruiting
        • Dorset County Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Fraser Witherow, MD
      • Kettering, United Kingdom, NN16 8UZ
        • Recruiting
        • Kettering General Hospital
        • Contact:
        • Principal Investigator:
          • Prashanth Raju, MD
      • Leicester, United Kingdom, LE3 9QP
        • Recruiting
        • Glenfield Hospital, Leicester
        • Contact:
        • Principal Investigator:
          • Bhavik Modi, MD
      • Liverpool, United Kingdom, L14 3PE
        • Recruiting
        • Liverpool Heart and Chest Hospital NHS Foundation Trust
        • Principal Investigator:
          • Joel Giblett, MD
        • Contact:
      • London, United Kingdom, SW3 6NP
        • Recruiting
        • Royal Brompton Hospital
        • Principal Investigator:
          • Ranil De Silva, MD
        • Contact:
      • London, United Kingdom, NW3 2QG
        • Recruiting
        • Royal Free Hospital
        • Contact:
        • Principal Investigator:
          • Tushar Kotecha, MD
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital
        • Contact:
        • Principal Investigator:
          • Jonathan Byrne, MD
      • London, United Kingdom, W12 0HS
        • Recruiting
        • Imperial College Healthcare NHS Trust
        • Contact:
        • Principal Investigator:
          • Rasha Al-Lamee, MD
      • London, United Kingdom, SE1 7EH
        • Recruiting
        • St. Thomas Hospital
        • Principal Investigator:
          • Tiffany Patterson, MD
        • Contact:
      • London, United Kingdom, E1 1FR
        • Recruiting
        • Barts Health Centre
        • Contact:
        • Principal Investigator:
          • Anthony Mathur, MD
      • London, United Kingdom, SW17 0QT
        • Recruiting
        • St. Georges University Hospital
        • Principal Investigator:
          • James Spratt, MD
        • Contact:
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Recruiting
        • Freeman Hospital
        • Contact:
        • Principal Investigator:
          • Bilal Bawamia, MD
      • Nottingham, United Kingdom, NG5
        • Recruiting
        • Nottingham University Hospital
        • Contact:
        • Principal Investigator:
          • Andrew Vanezis, MD
      • Oxford, United Kingdom, OX3 9DU
        • Recruiting
        • Oxford University Hospital
        • Contact:
        • Principal Investigator:
          • Giovanni De Maria, MD
      • Poole, United Kingdom, BH15 2JB
        • Recruiting
        • Royal Bournemouth Hospital
        • Contact:
        • Principal Investigator:
          • Peter O'Kane, MD
      • Taunton, United Kingdom, TA1 5DA
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic
        • Principal Investigator:
          • David Fortuin, MD
        • Contact:
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • Honorhealth Research Institute
        • Principal Investigator:
          • Taral Patel, MD
        • Contact:
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • University of Arizona Sarver Heart Center
        • Principal Investigator:
          • Michel Corban, MD
        • Contact:
    • California
      • Long Beach, California, United States, 90822
        • Withdrawn
        • Long Beach VA Medical Center
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai
        • Principal Investigator:
          • Suhail Dohad, MD
        • Contact:
      • San Diego, California, United States, 92037
        • Recruiting
        • UCSD
        • Principal Investigator:
          • Ehtisham Mahmud, MD
        • Contact:
      • San Francisco, California, United States, 94115
        • Recruiting
        • Kaiser Permanente San Francisco
        • Contact:
        • Principal Investigator:
          • Gopi Manthripragada
      • San Francisco, California, United States, 94117
        • Recruiting
        • UCSF
        • Principal Investigator:
          • Yousif Ahmad
        • Contact:
      • Thousand Oaks, California, United States, 91360
        • Recruiting
        • Los Robles Hospital and Medical Center
        • Principal Investigator:
          • Saibal Kar, MD
        • Contact:
    • Colorado
      • Littleton, Colorado, United States, 80120
        • Recruiting
        • South Denver Cardiology Associates
        • Contact:
        • Principal Investigator:
          • Lee McDonald
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Samit Shah, MD
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • MedStar Cardiovascular Research Network
        • Principal Investigator:
          • Hayder Hashim, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32605
        • Recruiting
        • The Cardiac and Vascular Institute
        • Principal Investigator:
          • Matheen Khuddus, MD
        • Contact:
      • Jacksonville, Florida, United States, 32209
        • Recruiting
        • UF Health Jacksonville
        • Contact:
        • Principal Investigator:
          • Daniel Soffer
      • Miami Beach, Florida, United States, 33140
        • Recruiting
        • Mount Sinai Miami
        • Contact:
        • Principal Investigator:
          • Nirat Beohar
      • Naples, Florida, United States, 34102
        • Recruiting
        • NCH Healthcare - Naples
        • Contact:
        • Principal Investigator:
          • Frank Adam
      • Pensacola, Florida, United States, 32504
      • Tallahassee, Florida, United States, 32308
        • Recruiting
        • Tallahassee Research Institute
        • Principal Investigator:
          • Thomas Noel, MD
        • Contact:
      • Tampa, Florida, United States, 33606
        • Recruiting
        • Tampa General - USF Cardiology
        • Principal Investigator:
          • Fadi Matar
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory Hospital
        • Contact:
        • Principal Investigator:
          • William Nicholson
      • Atlanta, Georgia, United States, 30342
        • Withdrawn
        • Northside Hospital
      • Gainsville, Georgia, United States, 30501
        • Recruiting
        • Northeast Georgia
        • Principal Investigator:
          • Olga Toleva
        • Contact:
      • Marietta, Georgia, United States, 30062
        • Recruiting
        • Wellstar Kennestone Hospital
        • Principal Investigator:
          • Salvatore Mannino
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Principal Investigator:
          • Dan Schimmel
        • Contact:
      • Springfield, Illinois, United States, 62781
        • Recruiting
        • Southern Illinois University
        • Principal Investigator:
          • Abdul Moiz Hafiz
        • Contact:
    • Indiana
      • Carmel, Indiana, United States, 46920
        • Recruiting
        • Ascension St. Vincent Heart Center
        • Contact:
        • Principal Investigator:
          • Bryce Lynn
      • Munster, Indiana, United States, 46321
        • Recruiting
        • Community Hospital - Munster
        • Principal Investigator:
          • Dean Ferrera
        • Contact:
          • Magdelena Borzecka
          • Phone Number: 2194007325
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Principal Investigator:
          • Prasad Gunasekaran
        • Contact:
      • Wichita, Kansas, United States, 67226
        • Withdrawn
        • Cardiovascular Research Institute of Kansas
    • Louisiana
      • Houma, Louisiana, United States, 70360
        • Recruiting
        • Cardiovascular Institute of the South
        • Contact:
        • Principal Investigator:
          • Vinod Nair
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Farouc Jaffer, MD
        • Contact:
      • Boston, Massachusetts, United States, 02120
      • Springfield, Massachusetts, United States, 01199
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Brett Wanamaker, MD
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Gerald Koenig
        • Contact:
      • Detroit, Michigan, United States, 48236
        • Recruiting
        • Henry Ford St. Johns
        • Principal Investigator:
          • Edouard Daher
        • Contact:
      • Grand Rapids, Michigan, United States, 59403
      • Southfield, Michigan, United States, 48075
        • Recruiting
        • Henry Ford Providence
        • Principal Investigator:
          • Shukri David, MD
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Recruiting
        • Minneapolis Heart Institute Foundation
        • Principal Investigator:
          • Jay Traverse
        • Contact:
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
        • Principal Investigator:
          • Amir Lerman, MD
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Recruiting
        • Jackson Heart Clinic
        • Principal Investigator:
          • William Crowder
        • Contact:
      • Tupelo, Mississippi, United States, 38801
        • Withdrawn
        • Cardiology Associates of North Mississippi
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • Saint Luke's Hospital
        • Contact:
        • Principal Investigator:
          • Anthony Hart, MD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University
        • Principal Investigator:
          • Haroon Faraz
        • Contact:
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Weill Cornell Medicine
        • Principal Investigator:
          • Jai Khatri
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center/NYPH
        • Principal Investigator:
          • Ajay Kirtane, MD
        • Contact:
      • New York, New York, United States, 10003
        • Recruiting
        • Mount Sinai Medical Center
        • Principal Investigator:
          • Samin Sharma, MD
        • Contact:
      • New York, New York, United States, 10010
      • Roslyn, New York, United States, 11576
        • Recruiting
        • St. Francis Hospital
        • Principal Investigator:
          • Evan Shlofmitz, MD
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
    • Ohio
      • Cincinnati, Ohio, United States, 45219
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Laura Young, MD
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University
        • Principal Investigator:
          • Scott Lilly, MD
        • Contact:
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
    • Oregon
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Heart Institute
        • Principal Investigator:
          • Jason Wollmuth, MD
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny General Hospital
        • Principal Investigator:
          • Mithun Chakravarthy
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • TriStar Centennial Medical Center
        • Principal Investigator:
          • Brian Jefferson, MD
        • Contact:
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt Heart
        • Principal Investigator:
          • Nadia Sutton, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78705
        • Recruiting
        • Ascension Texas Cardiovascular
        • Principal Investigator:
          • Mark Gajjar
        • Contact:
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas Health Science Center at Houston
        • Contact:
        • Principal Investigator:
          • Salman Arain, MD
      • Houston, Texas, United States, 77030
      • Houston, Texas, United States, 77030
        • Recruiting
        • Texas Heart Institute
        • Principal Investigator:
          • Emerson Perin
        • Contact:
      • Houston, Texas, United States, 77004
        • Withdrawn
        • HCA Houston Healthcare Medical Center
      • Plano, Texas, United States, 75093
        • Recruiting
        • The Heart Hospital Baylor Plano
        • Principal Investigator:
          • Srini Potluri
        • Contact:
      • San Antonio, Texas, United States, 78229
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Rajan Patel
        • Contact:
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Sentara Norfolk General Hospital
        • Principal Investigator:
          • Paul Lavigne, MD
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
      • Milwaukee, Wisconsin, United States, 53215
        • Recruiting
        • Advocate Aurora Research Institute
        • Contact:
          • Sara Klien
        • Principal Investigator:
          • Joaquin Solis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subject is older than 18 years of age
  2. 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 as determined by the local heart team and confirmed by a Central Screening Eligibility Committee Note: subjects may also have exertional dyspnea, but the symptoms that limit activity must be anginal in nature (including chest pain, pressure, heaviness, discomfort, with or without radiation to the neck, jaw, shoulders, arms, or other location) and not dyspnea
  3. Must have attempted treatment with the maximally tolerated dose of at least three of the four (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 at least 30 days prior to enrollment, must remain stable from enrollment to randomization, and there must be no intent to change the medical regimen for at least 12 months after randomization Note: If the dose of a medication was increased or decreased for a temporary period and then returned to the original dose, which will then be continued for at least 12 months after randomization, the subject may be immediately enrolled without needing to otherwise requalify
  4. 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 as determined by the local heart team, and confirmed by a Central Screening Eligibility Committee
  5. Evidence of either exercise or pharmacologically induced reversible ischemia severity by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFR-CT, FFR, iFR, or other non-hyperemic FDA approved tests (such as diastolic hyperaemia free ratio [DRF] or resting full-cycle ratio [RFR] in the distribution of the left coronary artery (LCA), performed within 12 months prior to enrollment 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 Note: The qualifying assessment must be performed after any myocardial infarction, CABG, or successful PCI within the prior 12 months. For subjects with multiple assessments, the one performed closest to enrollment will serve as the qualifying study
  6. 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 10 minutes, performed while the subject is maintained on their stable regimen of maximally tolerated doses of anti-anginal medications Note: The ETT variability must be less than 20% between last two ETTs performed.
  7. Left ventricular ejection fraction (LVEF) greater than or equal to 30% within the 12-months prior to enrollment Note: The LVEF must be reassessed after any intervening myocardial infarction. For subjects with multiple assessments, the most recent LVEF assessment is used as the qualifying test.
  8. Subject is willing and able to sign informed consent
  9. Subject is willing to comply with the specified follow-up evaluations

Angiographic Inclusion Criteria:

1) Three-vessel coronary angiography performed within 12 months prior to enrollment demonstrating obstructive CAD (visually estimated diameter stenosis of ≥70% or ≥50% - <70% with fractional flow reserve (FFR) value of ≤0.80 or an iFR or other FDA-approved/cleared non-hyperemic physiological assessment (such as DFR or RFR) of ≤0.89 in one or more lesions) in the left coronary artery (main epicardial vessels or branches) that is not suitable for and will not be treated with PCI or CABG as determined by the local heart team Note: The qualifying 3-vessel angiogram must be performed after any myocardial infarction, PCI, or CABG within the 12 months prior to enrollment. For patients with multiple 3-vessel angiograms, the one performed closest to enrollment will serve as the qualifying study

Exclusion Criteria:

  1. Recent (within 30 days prior to enrollment) troponin or CKMB positive acute coronary syndrome (NSTEMI or STEMI) Note: subjects with an elevated troponin or CKMB without acute coronary syndrome may still be enrolled

  2. Recent successful revascularization by either CABG or PCI within six months prior to enrollment

    Note: Successful revascularization is defined as any CABG procedure, or any PCI procedure with a reduction of one or more lesions to <50% diameter stenosis

    Note: Subjects with successful revascularization by either CABG or PCI that occurred less than six months prior to enrollment may still be approved for participation in the trial if revascularization was completed six months prior to procedure and CSEC approves subject participation

  3. Recent unsuccessful PCI (e.g., failed attempt to open a chronic total occlusion) within 30 days prior to enrollment

    Note: Subjects with unsuccessful PCI that occurred less than 30 days prior to enrollment may still be approved for participation in the trial if PCI was completed 30 days prior to procedure and CSEC approves subject participation

  4. The predominant manifestation of angina is dyspnea

    Note: some dyspnea may be present with exertion, but the predominant symptom that limits activity must be angina (i.e., chest pain, pressure, tightness, heaviness, or discomfort, with or without radiation to the neck, jaw, shoulders, arms, or other location)

  5. Has extra-coronary contributory causes of angina - e.g., untreated hyperthyroidism, untreated 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), or epicardial vasospasm disease/coronary artery vasospasm (CAS)/vasospastic angina (VSA)
  6. NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF during the 90 days prior to enrollment
  7. Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker
  8. 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
  9. Severe valvular heart disease (any valve)
  10. Moderate or severe RV dysfunction by echocardiography
  11. Pacemaker electrode/lead is present in the coronary sinus
  12. A Class I indication is present for an implantable defibrillator or cardiac resynchronization therapy according to ACCF/AHA/HRS guidelines
  13. Recent implantation of a new pacemaker or defibrillator lead with electrode in the right atrium within 90 days of enrollment
  14. Chronic severe renal failure (estimated eGFR less than 30 mL/min/1.73m2 by the MDRD formula) or subjects on chronic dialysis
  15. Known allergy to stainless steel or nickel
  16. 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 procedure)
  17. 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
  18. Pregnant or planning pregnancy within the next 12 months (women of reproductive potential must have a negative pregnancy test within 7 days of the procedure)
  19. 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.
  20. 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
  21. Comorbidities limiting life expectancy to less than one year
  22. Subject is currently hospitalized for definite or suspected COVID-19
  23. Subject has previously been symptomatic with or hospitalized for COVID-19 and has been asymptomatic for <8 weeks prior to enrollment or has not returned to his or her prior baseline (pre-COVID-19) clinical condition
  24. Subject is asymptomatic but has had a positive PCR or antigen test for COVID-19 within the past 4 weeks prior to enrollment

Angiographic/Hemodynamic Exclusion Criteria:

1) Coronary anatomy amenable to revascularization of ischemic myocardial territory by either PCI or CABG with at least moderate likelihood of long-term alleviation of angina or angina equivalent symptoms, as per the assessment of the local heart team.

Note: If a pathway to coronary revascularization is present which, in the opinion of the local heart team, is reasonably low risk and reasonably likely to provide long-term symptom relief and the subject refuses the revascularization procedure, the patient is ineligible for randomization

Procedural Angiographic/Hemodynamic Randomization Exclusion Criteria:

  1. Mean right atrial pressure greater than 15 mmHg assessed during the final screening procedure for eligibility assessment and potential randomization
  2. Anomalous or abnormal CS anatomy (e.g., tortuosity, aberrant branch, persistent left superior vena cava [SVC]) as demonstrated by angiogram
  3. The CS diameter at the most proximal end of the planned implant region (2-4 cm distal to the coronary sinus ostium) is less than 9.5 mm or greater than 13.0 mm

Single-arm Registry (Unblinded, Non-Randomized Treatment Arm) Inclusion/Exclusion Criteria:

Subject can be included in the single-arm registry if they fall into one of the three categories with inclusions and exclusion criteria as described below.

Predominant right coronary disease subjects (RCA):

  1. Reversible ischemia: Subjects with evidence of either exercise or pharmacologically induced reversible ischemia by stress echo, nuclear study, PET, perfusion MRI, CT perfusion, FFR-CT, FFR, iFR, or other non-hyperemic FDA approved or cleared tests (such as DFR or RFR) in the distribution of the right coronary artery (RCA), performed within 12 months prior to enrollment.

    Note: If the subject has evidence of ischemia in both the LCA and RCA distributions, the extent of ischemia must be greater in the RCA distribution

    Note: The qualifying assessment must be performed after any myocardial infarction, CABG, or successful PCI within the prior 12 months. If the anti-anginal medication regimen is permanently changed after the assessment of ischemia, the test must be repeated. For subjects with multiple assessments, the one performed closest to enrollment will serve as the qualifying study

  2. Obstructive CAD: Three-vessel coronary angiography performed within the 12 months prior to enrollment demonstrating obstructive CAD (visually assessed diameter stenosis of ≥70% or ≥50% - <70% with fractional flow reserve (FFR) value of ≤0.80 or an iFR or other FDA-approved/cleared non-hyperemic physiological assessment (such as DFR or RFR) of ≤0.89 in one or more lesions) in the RCA (main epicardial vessels or branches) that is not suitable for and will not be treated with PCI or CABG as determined by the local heart team.

    Note: The qualifying assessment must be performed after any myocardial infarction, PCI or CABG within the prior 12 months. For subjects with multiple assessments, the one performed closest to enrollment will serve as the qualifying study

  3. In addition to the above inclusion criteria, subjects must meet all inclusion criteria (except clinical inclusion #5 and angiographic inclusion #1) and none of the exclusion criteria of the main randomized trial

Non-obstructive coronary artery disease subjects (ANOCA)

  1. Abnormal Coronary Flow Reserve (CFR): subjects must have either abnormal PET CFR (< 2.0), abnormal perfusion CMR (cardiac MRI) CFR (<1.85), or abnormal invasive CFR (<2.5) in at least one main epicardial coronary artery performed within 12 months prior to enrollment

    Note: Subjects may or may not have evidence of either exercise or pharmacologically induced reversible ischemia by stress echo, nuclear study, PET, perfusion MRI, or CT perfusion

  2. Non-obstructive CAD: subjects have non-obstructive coronary disease (estimated diameter stenosis in all coronary lesions is <50% and (if performed) FFR ≥0.81 or a non-hyperemic test is ≥0.90) demonstrated on three-vessel coronary angiography performed within the 12 months prior to enrollment. If an estimated diameter stenosis is ≥50% to <70%, the patient may still qualify if FFR ≥0.81 or a non-hyperemic test is ≥0.90 in that vessel. If both FFR and a non-hyperemic test are performed, both must be negative.

    Note: The qualifying 3-vessel angiogram must be performed after any myocardial infarction, PCI or CABG within the 12 months prior to enrollment. For patients with multiple 3-vessel angiograms, the one performed closest to enrollment will serve as the qualifying study

  3. In addition to the above inclusion criteria, subjects must meet all inclusion criteria (except clinical inclusion #5 and angiographic inclusion #1) and none of the exclusion criteria of the main randomized trial

Subjects unable to complete ETT

  1. Subjects must be unable to complete the required COSIRA-II exercise tolerance test due to lower limb amputation (above the ankle) or other physiologic condition with documented chronic mobility or balance issues that require the use of a walking aid (e.g., wheelchair, cane, rollator, crutches, or knee walker).
  2. In addition to the above inclusion criteria, subjects must meet all inclusion criteria (except clinical inclusion #6) and none of the exclusion criteria of the main randomized trial

Prior to inclusion in single-arm registry, all subjects will be reviewed by the Central Screening Eligibility Committee to ensure that they meet registry inclusion criteria and are not eligible for enrollment into the randomized study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1 (treatment arm):Implantation of the Reducer device
Device: Arm 1: treatment with Shockwave Reducer
Shockwave 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
Other: Arm 3 (unblinded, non-randomized): Single Arm Registry
Device: Arm 3 (unblinded, non-randomized): Single arm registry
Shockwave Reducer is an implantable device being evaluated for the alleviation of refractory angina symptoms

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Co-Primary Effectiveness Endpoints
Time Frame: 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.

Change in SAQ clinical summary score assessed at 6 months post procedure compared to baseline in the Treatment arm compared to the Sham-control arm.
6 months
Primary Safety Endpoints
Time Frame: 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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Canadian Cardiovascular Society (CCS) Angina Score
Time Frame: 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).
6 months
Canadian Cardiovascular Society (CCS) Angina Score
Time Frame: 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).
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Canadian Cardiovascular Society (CCS) Angina Score
Time Frame: 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).
12 months, 2 years, 3 years, 4 years, and 5 years
Angina Burden
Time Frame: 6 and 12 months
Angina frequency and burden compared to baseline
6 and 12 months
Activity
Time Frame: 6 and 12 months
Measure of activity assessed by actigraphy compared to baseline
6 and 12 months
Exercise Tolerance Testing
Time Frame: 6 and 12 months
Change in ETT parameters compared to baseline
6 and 12 months
Exercise Tolerance Testing
Time Frame: 12 months
Change in total exercise duration compared to baseline
12 months
Exercise Tolerance Testing
Time Frame: 6 and 12 months
Total exercise duration
6 and 12 months
Doctor Visits
Time Frame: 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 (for angina, non-angina cardiovascular causes) post procedure compared to baseline
6 months, 12 months, 2 years, 3 years, 4 years, and 5 years
Adverse Events
Time Frame: 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
30 day, 6 month, 12 month, 2 years, 3 years, 4 years, and 5 years
Seattle Angina Questionnaire (SAQ) Score
Time Frame: 6 month, 12 month, 2 years, 3 years, 4 years, and 5 years
Change in other Seattle Angina Questionnaire (SAQ) domain scores and clinical summary score at 6 months (primary endpoint), 12 month and annually post procedure 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.
6 month, 12 month, 2 years, 3 years, 4 years, and 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shockwave Medical, Inc.

Collaborators

Shockwave Medical, Inc.

Investigators

  • Principal Investigator: Timothy D Henry, MD, The Christ Hospital Health Network
  • Principal Investigator: Gregg W Stone, MD, Mt. Sinai Heart Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 4, 2022

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

January 1, 2032

Study Registration Dates

First Submitted

October 8, 2021

First Submitted That Met QC Criteria

October 21, 2021

First Posted (Actual)

November 1, 2021

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 022-REDUCLN-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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