Efficacy of the COronary SInus Reducer in Patients With Refractory Angina II
Overview
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Shockwave Medical, Inc.
- Enrollment
- 380
- Locations
- 159
- Primary Endpoint
- Effectiveness
Overview
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.
Detailed Description
The COSIRA-II study is a multicenter, randomized (1:1 ratio), double-blinded, sham-controlled clinical trial.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Angiographic Inclusion Criteria:
Exclusion Criteria
- •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)
- •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)
- •NYHA Class III or IV heart failure (HF), decompensated HF or hospitalization due to HF during the 90 days prior to enrollment
Arms & Interventions
Arm 1 (treatment arm):Implantation of the Reducer device
Intervention: Arm 1: treatment with Shockwave Reducer (Device)
Arm 2 (sham-control arm): Control (no device implantation)
Intervention: Arm 2 (control): Implantation procedure with no device implanted (Other)
Arm 3 (unblinded, non-randomized): Single Arm Registry
Intervention: Arm 3 (unblinded, non-randomized): Single arm registry (Device)
Outcomes
Primary Outcomes
Effectiveness
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.
Safety Events
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.
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.
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.
Secondary Outcomes
- Seattle Angina Questionnaire (SAQ) Score(6 months)
- Canadian Cardiovascular Society (CCS) Angina Score(6 months)