Cardiogenic Shock, Mitral Regurgitation
Conditions
Brief summary
Mitral regurgitation may be seen in the setting of cardiogenic shock. Transcatheter edge-to-edge repair (TEER) has been shown to improve outcomes in patients with chronic heart failure. Observational studies suggest improvements in clinical outcomes in patients with mitral regurgitation in the setting of cardiogenic shock; however, there remains a lack of randomized clinical data to support the use of TEER in cardiogenic shock. This study will be a multicenter, open-label, randomized-controlled trial with two study arms: medical therapy and TEER. Patients admitted to the Cardiac Intensive Care Unit (CICU), Cardiac Surgery Intensive Care Unit (CSICU) or Intensive Care Units (ICU) at participating centers will be recruited. The study aims to answer the question: "Does TEER in patients with SCAI stage C or D cardiogenic with concomitant moderate or greater mitral regurgitation improve outcomes as compared to medical therapy?" The study hypothesis is that TEER will lead to an overall improvement in the composite outcome as compared to the medical therapy arm.
Detailed description
Current management strategies for patients with SCAI stage C through E cardiogenic shock include management in a cardiac intensive care unit (CICU) or cardiac surgery intensive care unit (CSICU) with intravenous inotropes (i.e. medications to increase the pumping function of the heart), vasopressors (i.e. medications to increase blood pressure), ventilatory support, and/or mechanical circulatory support. Importantly, with the exception of revascularization, little data exists demonstrating the ability to alter prognosis in patients with cardiogenic shock. Mitral regurgitation may be seen in the setting of cardiogenic shock. Transcatheter edge-to-edge repair (TEER) has been shown to improve outcomes in patients with chronic heart failure. Observational studies suggest improvements in clinical outcomes in patients with mitral regurgitation in the setting of cardiogenic shock; however, there remains a lack of randomized clinical data to support the use of TEER in cardiogenic shock. This study will be divided into two phases, as follows: Phase 1 (Vanguard) - The first phase of this study will be composed of a feasibility stage where a total of 10 participants from centers in Ontario, Canada will be recruited. The primary objective of this phase is to ascertain feasibility of participant recruitment and treatment. Feasibility would be considered met if 10 participants were enrolled 12 months from the date of activation of all four centers. Phase 2 - The second phase of this study will be a continuation of Phase 1 where the remaining 134 participants, for a total of 144 participants in the overall study. For this second phase of the study, patients will be recruited from high-volume TEER centers in Canada and the United States - with participating centers performing more than 25 TEER procedures per year. Eligible participants will be randomly assigned in a 1:1 fashion to the medical therapy arm (i.e. control arm) or the TEER arm (i.e. intervention arm) of the trial.
Interventions
Transcatheter edge-to-edge repair
OTHERMedical therapy
Medical treatment in an intensive care unit
Sponsors
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants or substitute decision maker is able and willing to provide written informed consent 2. Age ≥ 18 years 3. SCAI stage C or D cardiogenic shock with persistent inotrope/vasopressor/non-durable mechanical support or unable to wean ventilatory support due to pulmonary edema for 24 hours prior to randomization 4. Greater than or equal to 3+ MR as determined by a study center's transesophageal echocardiogram (TEE) 5. In the opinion of the study center's heart team the participant is anatomically eligible for TMVr with the potential to achieve \<3+ MR
Exclusion criteria
1. Unwilling or unable to obtain informed consent from the participant or substitute decision maker 2. Revascularization of coronary artery disease performed in the 48 hours prior to randomization 3. If the mechanism of MR is deemed to be degenerative, in the opinion of the heart team the participant is eligible for surgical intervention 4. Prior mitral valve leaflet surgery or implanted mitral valve prosthesis (excluding ring) 5. Echocardiographic evidence of left sided intracardiac mass or thrombus 6. Diagnosis of active infective endocarditis 7. Transesophageal echocardiogram is contraindicated 8. Mitral valve anatomy deemed contraindication to TMVr implantation that cannot be addressed procedurally as determined by the study center's heart team 9. Any aortic valve disease greater than moderate in severity 10. A known hypersensitivity or contraindication to procedure medications which cannot be adequately managed medically 11. Out of hospital cardiac arrest or in-hospital cardiac arrest without documented neurologic recovery 12. Plan for durable mechanical circulatory support implantation prior to TMVr 13. In the opinion of the treating team, there is a significant comorbidity that would limit life expectancy in hospital 14. Pregnant or planning to become pregnant in the next 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary composite outcome | Through duration of hospitalization, generally up to 12 weeks following admission | The primary outcome in this clinical trial will be a composite of in-hospital all-cause mortality, cardiac transplantation, implantation of durable LVAD, or discharge on palliative inotropic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In hospital all-cause mortality | Through duration of hospitalization, generally up to 12 weeks following admission | Death from any cause |
| In hospital implantation of durable left-ventricular assist device or cardiac transplantation | Through duration of hospitalization, generally up to 12 weeks following admission | Implantation of durable left-ventricular assist device or cardiac transplantation |
| Discharge on inotropes | Through duration of hospitalization, generally up to 12 weeks following admission | Discharge from index hospitalization on palliative inotropic therapy |
| Residual mitral regurgitation | Through duration of hospitalization, generally up to 12 weeks following admission | Severity of residual mitral regurgitation as assessed by the core lab on last available in hospital echocardiogram |
| Technical success | Measured at exit from procedure room, generally 2 hours after implant | All of the following must be present: I. Absence of procedural mortality II. Successful access, delivery, and retrieval of the device delivery system III. Successful deployment and correct positioning of the first intended device IV. Freedom from emergency surgery or reintervention related to the device or access procedure. |
| Device success | At time of discharge from hospitalization, generally up to 12 weeks following admission | All of the following must be present: I. Absence of procedural mortality or stroke II. Proper placement and positioning of the device III. Freedom from unplanned surgical or interventional procedures related to the device or access procedure IV. Continued intended safety and performance of the device, including: A. No evidence of structural or functional failure B. No specific device-related technical failure issues and complications C. Reduction of mitral regurgitation to either optimal or acceptable levels without significant mitral stenosis, and with no greater than mild (1+) paravalvular mitral regurgitation (and without associated hemolysis) |
| Stroke or transient ischemic attack | Through duration of hospitalization, generally up to 12 weeks following admission | Acute episode of a focal or global neurological deficit as determined by or in conjunction with the designated neurologist |
| Bleeding | Through duration of hospitalization, generally up to 12 weeks following admission | * Any intracranial bleeding (excluding microhemorrhages \<10 mm evident only on gradient-echo MRI) * Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in hematocrit * Fatal bleeding (bleeding that directly results in death within 7 d) |
| Vascular access complications | Through duration of hospitalization, generally up to 12 weeks following admission | Access site-related arterial or venous injury or injury to surrounding structures |
| Cardiac structural complications | Through duration of hospitalization, generally up to 12 weeks following admission | Cardiac perforation or pseudoaneurysm |
Countries
Canada, United States
Contacts
CONTACTBenjamin Hibbert, MD PhD
CONTACTPietro Di Santo, MD
Outcome results
None listed