Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II

NCT05102019 | Recruiting DMC FDA Device

• 1 other identifier: 022-REDUCLN-002
• Study Type: interventional
• Target: 380
• Locations: 3 countries
• Sites: 95

Brief Summary

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.

Conditions

Refractory Angina

Outcome Measures

Primary Outcomes (2)

• Co-Primary Effectiveness Endpoints

  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

  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 Outcomes (2)

• Canadian Cardiovascular Society (CCS) Angina Score

  6 months

• Canadian Cardiovascular Society (CCS) Angina Score

  6 months

Other Outcomes (9)

• Canadian Cardiovascular Society (CCS) Angina Score

  12 months, 2 years, 3 years, 4 years, and 5 years

• Angina Burden

  6 and 12 months

• Activity

  6 and 12 months

Study Arms (3)

Arm 1 (treatment arm):Implantation of the Reducer device

EXPERIMENTAL

Device: Arm 1: treatment with Shockwave Reducer

Arm 2 (sham-control arm): Control (no device implantation)

SHAM COMPARATOR

Other: Arm 2 (control): Implantation procedure with no device implanted

Arm 3 (unblinded, non-randomized): Single Arm Registry

OTHER

Device: Arm 3 (unblinded, non-randomized): Single arm registry

Interventions

Arm 3 (unblinded, non-randomized): Single arm registry DEVICE

Shockwave Reducer is an implantable device being evaluated for the alleviation of refractory angina symptoms

Arm 3 (unblinded, non-randomized): Single Arm Registry

Arm 1: treatment with Shockwave Reducer DEVICE

Shockwave reducer is an implantable device being evaluated for the alleviation of refractory angina symptoms

Arm 1 (treatment arm):Implantation of the Reducer device

Arm 2 (control): Implantation procedure with no device implanted OTHER

No device is implanted

Arm 2 (sham-control arm): Control (no device implantation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is older than 18 years of age
• 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
• 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
• 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
• 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
• 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.
• 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.
• Subject is willing and able to sign informed consent
• Subject is willing to comply with the specified follow-up evaluations
• \) 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

You may not qualify if:

• 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
• 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
• 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
• 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)
• NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF during the 90 days prior to enrollment
• Life threatening rhythm disorders or any rhythm disorders that would require future placement of an internal defibrillator and/or pacemaker
• 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
• Severe valvular heart disease (any valve)
• Moderate or severe RV dysfunction by echocardiography
• Pacemaker electrode/lead is present in the coronary sinus
• A Class I indication is present for an implantable defibrillator or cardiac resynchronization therapy according to ACCF/AHA/HRS guidelines

Sponsors & Collaborators

• Shockwave Medical, Inc.: lead

Study Sites (95)

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

University of Arizona Sarver Heart Center

Tucson, Arizona, 85724, United States

RECRUITING

Long Beach VA Medical Center

Long Beach, California, 90822, United States

WITHDRAWN

Cedars-Sinai

Los Angeles, California, 90048, United States

RECRUITING

UCSD

San Diego, California, 92037, United States

RECRUITING

Kaiser Permanente San Francisco

San Francisco, California, 94115, United States

RECRUITING

UCSF

San Francisco, California, 94117, United States

RECRUITING

Los Robles Hospital and Medical Center

Thousand Oaks, California, 91360, United States

RECRUITING

South Denver Cardiology Associates

Littleton, Colorado, 80120, United States

RECRUITING

Yale University

New Haven, Connecticut, 06519, United States

RECRUITING

MedStar Cardiovascular Research Network

Washington D.C., District of Columbia, 20010, United States

RECRUITING

The Cardiac and Vascular Institute

Gainesville, Florida, 32605, United States

RECRUITING

UF Health Jacksonville

Jacksonville, Florida, 32209, United States

RECRUITING

Mount Sinai Miami

Miami Beach, Florida, 33140, United States

RECRUITING

NCH Healthcare - Naples

Naples, Florida, 34102, United States

RECRUITING

Ascension Sacred Heart

Pensacola, Florida, 32504, United States

RECRUITING

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

RECRUITING

Tampa General - USF Cardiology

Tampa, Florida, 33606, United States

RECRUITING

Emory Hospital

Atlanta, Georgia, 30308, United States

RECRUITING

Northside Hospital

Atlanta, Georgia, 30342, United States

WITHDRAWN

Northeast Georgia

Gainsville, Georgia, 30501, United States

RECRUITING

Wellstar Kennestone Hospital

Marietta, Georgia, 30062, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Southern Illinois University

Springfield, Illinois, 62781, United States

RECRUITING

Ascension St. Vincent Heart Center

Carmel, Indiana, 46920, United States

RECRUITING

Community Hospital - Munster

Munster, Indiana, 46321, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Cardiovascular Research Institute of Kansas

Wichita, Kansas, 67226, United States

WITHDRAWN

Cardiovascular Institute of the South

Houma, Louisiana, 70360, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

RECRUITING

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Henry Ford St. Johns

Detroit, Michigan, 48236, United States

RECRUITING

Corewell Health

Grand Rapids, Michigan, 59403, United States

RECRUITING

Henry Ford Providence

Southfield, Michigan, 48075, United States

RECRUITING

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Jackson Heart Clinic

Jackson, Mississippi, 39216, United States

RECRUITING

Cardiology Associates of North Mississippi

Tupelo, Mississippi, 38801, United States

WITHDRAWN

Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

RECRUITING

Hackensack University

Hackensack, New Jersey, 07601, United States

RECRUITING

Mount Sinai Medical Center

New York, New York, 10003, United States

RECRUITING

NYU Langone

New York, New York, 10010, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

Columbia University Medical Center/NYPH

New York, New York, 10032, United States

RECRUITING

St. Francis Hospital

Roslyn, New York, 11576, United States

RECRUITING

Novant Health

Charlotte, North Carolina, 28204, United States

RECRUITING

The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Ascension St. John

Tulsa, Oklahoma, 74104, United States

RECRUITING

Providence Heart Institute

Portland, Oregon, 97225, United States

RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

TriStar Centennial Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt Heart

Nashville, Tennessee, 37232, United States

RECRUITING

Ascension Texas Cardiovascular

Austin, Texas, 78705, United States

RECRUITING

Medical City Fort Worth

Fort Worth, Texas, 76104, United States

RECRUITING

HCA Houston Healthcare Medical Center

Houston, Texas, 77004, United States

WITHDRAWN

Houston Methodist

Houston, Texas, 77030, United States

RECRUITING

Texas Heart Institute

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

The Heart Hospital Baylor Plano

Plano, Texas, 75093, United States

RECRUITING

Methodist Hospital of San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Advocate Aurora Research Institute

Milwaukee, Wisconsin, 53215, United States

RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V521M9, Canada

RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, K1y4W7, Canada

RECRUITING

Toronto General Hospital (UHN)

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

CHUM

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

IUCPQ-Ulaval

Québec, Quebec, G1V4G5, Canada

RECRUITING

Essex Cardiothoracic Centre

Basildon, SS16 5NL, United Kingdom

RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, B15 2GW, United Kingdom

RECRUITING

Bristol Heart Institute

Bristol, BS2 8HW, United Kingdom

RECRUITING

Royal Papworth Hospital

Cambridge, |CB2 0AY, United Kingdom

RECRUITING

Dorset County Hospital NHS Foundation Trust

Dorchester, DT1 2JY, United Kingdom

RECRUITING

Kettering General Hospital

Kettering, NN16 8UZ, United Kingdom

RECRUITING

Glenfield Hospital, Leicester

Leicester, LE3 9QP, United Kingdom

RECRUITING

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, L14 3PE, United Kingdom

RECRUITING

Barts Health Centre

London, E1 1FR, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

St. Thomas Hospital

London, SE1 7EH, United Kingdom

RECRUITING

King's College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

St. Georges University Hospital

London, SW17 0QT, United Kingdom

RECRUITING

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

RECRUITING

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Nottingham University Hospital

Nottingham, NG5, United Kingdom

RECRUITING

Oxford University Hospital

Oxford, OX3 9DU, United Kingdom

RECRUITING

Royal Bournemouth Hospital

Poole, BH15 2JB, United Kingdom

RECRUITING

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

RECRUITING

Related Publications (2)

• Verheye S, Jolicoeur EM, Behan MW, Pettersson T, Sainsbury P, Hill J, Vrolix M, Agostoni P, Engstrom T, Labinaz M, de Silva R, Schwartz M, Meyten N, Uren NG, Doucet S, Tanguay JF, Lindsay S, Henry TD, White CJ, Edelman ER, Banai S. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015 Feb 5;372(6):519-27. doi: 10.1056/NEJMoa1402556.

  PMID: 25651246 BACKGROUND

• Bober RM, Johnson NP. How might coronary sinus reducer treatment change myocardial perfusion? J Nucl Cardiol. 2024 Mar;33:101828. doi: 10.1016/j.nuclcard.2024.101828. Epub 2024 Feb 21. No abstract available.

  PMID: 38395338 DERIVED

MeSH Terms

Conditions

Angina Pectoris

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Timothy D Henry, MD

  The Christ Hospital Health Network

  PRINCIPAL INVESTIGATOR

• Gregg W Stone, MD

  Mt. Sinai Heart Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

COSIRA-II Study Team

CONTACT

Fax: 1-888-887-8097; connect.cosira2@shockwavemedical.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: November 1, 2021
• Study Start: January 4, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2032
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (70); CA (5); GB (20)