SynCardia 70cc TAH-t for Destination Therapy (DT)

On 15 October 2004, the SynCardia temporary Total Artificial Heart (TAH-t) received Food and Drug Administration (FDA) approval (Premarket Approval Application \[PMA\] #P030011) for in-hospital use as a bridge to transplant (BTT) in cardiac transplant-eligible candidates at risk of imminent death from biventricular failure. On 2 March 2012, FDA granted a Humanitarian Use Designation (HUD) to the 70cc TAH-t System for use as Destination Therapy (DT) in patients at risk of imminent death from irreversible biventricular heart failure who are not eligible for transplant and have a body surface area (BSA) \>1.7m. This clinical study is intended to determine the safety and probable benefit of the 70cc TAH-t for use in DT and support a Humanitarian Device Exemption (HDE) application for this new indication for the TAH-t System. The SynCardia TAH-t System is a pulsatile biventricular device that replaces a patient's native ventricles and valves by pumping blood to both the pulmonary and systemic circulation. The TAH-t System for DT consists of the implantable TAH-t with SynHall Valves, powered by PMA-approved external pneumatic drivers \[the Circulatory Support System (CSS) Console, the Companion 2 Driver System and the Freedom Driver System\]. The TAH-t System is intended to be implanted in the operating room by a qualified surgeon and is capable of supporting the patients both inside and outside the hospital. The SynCardia TAH-t for DT is indicated for refractory advanced heart failure patients with biventricular failure who are not candidates for cardiac transplant because of the presence of contraindications to transplant, including cancer, advanced age, obesity, end-stage diabetes mellitus, high panel reactive antibodies (PRAs), non-cardiac congenital defects, contraindications to immunosuppression, lack of social support, poor medical compliance, neurological impairment or other co-morbidities with a poor prognosis for survival. Patients with life-threatening, irreversible biventricular failure who are not eligible for transplant currently have no alternative but death. The rationale for conducting this study is based on the results of clinical studies in the bridge-to-transplant (BTT) patient population, together with the in vitro design verification and validation testing, in vitro reliability testing, and clinical reliability experience of more than thirty years. The study design is a prospective, non-randomized, two-treatment arm, multi-center study. Nineteen (19) patients will be enrolled in the Primary Arm at up to 30 investigational sites to support an HDE for the use of the TAH-t as DT. Up to an additional 19 patients may be enrolled in the Secondary Arm to futher characterize the use of the TAH-t for DT in a broader patient population. Patients treated with the 70cc TAH-t System for DT under the Primary Arm will be adult male and female patients between the ages of 19 and 75 years old with a BSA ≥1.7m2 with life-threatening irreversible biventricular failure who are not eligible for a heart transplant (as determined by the implanting center at the time of implant assessment) and who meet the enrollment criteria defined in the clinical protocol. Patients treated with the 70cc TAH-t System for DT under the Secondary Arm will be adult male and female patients who are at least 19 years old, are not eligible for a heart transplant (as determined by the implanting center at the time of implant assessment), and who meet the less restrictive enrollment criteria defined in the clinical protocol. The risks to which the TAH-t subjects will be exposed in this clinical investigation are expected to be no more than the well-characterized risks of the PMA-approved TAH-t System when used for the bridge-to-transplant population and have been mitigated by the design and testing of the TAH-t System. The primary objective of the SynCardia temporary Total Artificial Heart (TAH-t) for DT Study is to evaluate whether the TAH-t can support patients with life-threatening irreversible biventricular heart failure who are ineligible for cardiac transplantation (as determined by the implanting center at time of implant screening assessment), without experiencing permanent disabling stroke-related deficits (as evidenced by a Modified Rankin Scale score of 0 - 2). The other primary objective of the study is to evaluate whether the safety profile of the device, when used for DT, is acceptable. Probable benefit is defined as survival to six months on TAH-t System support with the same implanted TAH-t, without experiencing permanent disabling stroke-related deficits. This patient population, without treatment, has a poor prognosis of survival. Per M.L.A. Haeck, "Patients with drug refractory end-stage HF \[heart failure\] receiving support with inotropic drugs \[have\] a 3-, 6-, and 12-month survival of 51%, 26%, and 6%, respectively, with a mean survival of only 3.4 months."1 The study success criteria are: alive on the original TAH-t and free from permanent disabling stroke-related deficits (as evidenced by Modified Rankin Scale score of 0 - 2) at six months post-implant (or transplanted prior to six months post-implant). For the study to be considered a success, eight of the 19 subjects either must be alive at six months on the original TAH-t implant, without experiencing a permanent disabling stroke deficit, or have become transplant eligible (or have been transplanted). The safety endpoints will be captured according to the Intermacs Registry AE definitions and will be assessed according to the same data collection schedule followed under the Intermacs Registry protocol. Secondary safety endpoints will be the incidences of major infection (sepsis), neurological events (ischemic or hemorrhagic cardiovascular accident \[CVA\]), chronic renal dysfunction, and the rate of major device failures/malfunctions, each defined per the Intermacs definitions. A performance goal for each has been established based on the previous experience of TAH-t patients who were waiting for a heart transplant. All subjects will be followed in the study from the date of TAH-t implant until six months post-implant, cardiac transplantation, death, or withdrawal from study, whichever occurs first. Data from the six month post-TAH-t implant period will be used to support an HDE application. After the six month follow-up visit, patients will continue to be followed under the study for up to five (5) years post-TAH-t implant \[every six months for up to two years while supported with the TAH-t implant and then annually for another three years\]. 1 Neth Heart J (2012) 20:167-175 15 November 2011