Circulatory Support in Pediatric Heart Failure Patients Using the Jarvik 2015 VAD: A Feasibility Study
Study ID: STU 112017-032
Study Design : Two prospective, single-arm feasibility studies; one with Standard Cardiac anatomy and one with Challenging Cardiac anatomy STuDY DeSiGn: This study consists of two prospective, multi-center, single-arm feasibility studies; one in patients with Standard Cardiac anatomy and one in patients with Challenging Cardiac anatomy to evaluate the performance of the Jarvik 2015 VaD in pediatric patients with severe heart failure. Five Standard Cardiac anatomy subjects reaching endpoints along with 5 Challenging Cardiac anatomy subjects reaching endpoints will be enrolled over approximately an 18 month period. The primary endpoints will be assessed at the time of clinical endpoint defined in section 4.1.1. The study design is shown in Figure 5.1. Study Measures This section describes how measurements will be made to quantify the trial endpoints. The timing of the measurements is described in Sections 7.1-7.2. Measures of Safety a. Primary endpoint PediMaCS-defined (version 5.0)16 aes will be reported for each implanted patient along with relationship to the investigational device and implant procedure for each cohort. b. Secondary endpoints The secondary measures of safety include neurologic, functional and cognitive status, and ability to de-intensify concomitant support, as well as brain MRi performed 12 months post-explant. Based on limited prior experience with VaDs , stroke, bleeding and infection are common adverse events with currently available devices. The objective of measuring adverse events in detail (in particular neurological events) and quality of life is that a device that demonstrates similar survival but fewer complications or improved quality of life could have important advantages to patients requiring long-term support over commercially available devices. The objective of neurologic assessments in this trial is to measure the incidence and severity of stroke with the investigational Jarvik 2015 VaD. Follow-up to 180 days post-implant will be used for survivors with the Jarvik 2015 VaD in place and follow-up up to 12 months following explant will be used otherwise to calculate the incidence rate. Measures include: - PediMaCS-defined aes possibly, probably, or definitely related to the device while the device is in place - PediMaCS-defined neurologic impairment. a qualifying neurologic event must meet the criteria denoted in the proposed revised PediMaCS definition (version 5.0), which is: any new, temporary or permanent, focal or global neurologic dysfunction ascertained by a standard neurological history and examination administered by a neurologist or other qualified physician and documented with appropriate diagnostic tests and consultation note; or an abnormality identified by surveillance neuroimaging. The examining physician will classify the event as a cerebrovascular event as defined below or as a non-vascular acute neurologic event. a neurologic event may be recognized by a clinically evident sign or symptom, or by clinically-silent electrographic seizure activity, or as a clinically silent lesion detected by surveillance neuroimaging. each neurologic event should be classified by the clinical provider following complete neurologic assessment as one of the following event types: 1) Transient ischemic attack, 2) ischemic stroke 3) acute symptomatic intracranial hemorrhage 4) Clinically covert ischemic stroke or iH 5) Hypoxic-ischemic encephalopathy, defined as acute new encephalopathy*** due to hypoxic-ischemic injury (Hie), manifest as clinically- evident signs or symptoms, or subclinical electrographic seizures found by complete neurological diagnostic evaluation to be attributable to acute global or focal hypoxic or ischemic brain injury not meeting one of ischemic stroke or iH events as defined above. 6) acute new encephalopathy
Children must meet all of the following criteria: 1. Males and females within weight range not less than 8.0 Kg, and not more than 30.0 Kg 2. Body surface area (BSA) not less than 0.4 m2 and not more than 1.0 m2 3. Cardiac anatomy categories: a. Standard Cardiac Anatomy: Two-ventricle circulation, including cardiomyopathy, repaired structural heart disease (e.g. anomalous left coronary artery from the pulmonary artery [ALCAPA], aortic stenosis) or acquired heart disease (e.g., myocarditis, Kawasaki disease) b. Challenging Cardiac Anatomy: Any challenging cardiac anatomy (including but not limited to single ventricle heart disease, RCM, HCM3-5) that, in the opinion of the investigator with confirmation from the PumpKIN Executive Committee, is difficult to support with available (e.g. pulsatile) devices. 4. INTERMACS Profile 1 or 2 as evidenced by: a. Inability to wean from extra-corporeal membrane oxygenation (ECMO) or other temporary circulatory support (TCS), OR b. Inability to wean from mechanical ventilator support, OR c. Inotrope-dependent, decompensated heart failure AND meet one or more of the following criteria within 48 hours prior to implant (unless otherwise noted) which is attributed to decompensated heart failure despite optimal medical therapy: i. Urine output <0.5 cc/kg/hour for 12hr within 48 hours ii. Creatinine level >2 times the upper limit of normal (ULN) for age iii. Alaninee aminotransferase (ALT) or total bilirubin result >3 times the ULN for age (either qualifies the patient) iv. Mixed venous oxygen saturation (SvO2) <55% (or arteriovenous oxygen different >45%) in two repeated measurements v. Acidosis: Base excess >-5 in 2 or more measurements vi. Inability to tolerate appropriate enteral calories as prescribed by a registered dietician vii. Inability to ambulate freely to participate fully in age-appropriate activities of daily living (ADLs) and/or cardiac rehabilitation/physical therapy, OR 5. Potentially eligible (i.e., no medical or surgical contraindications) to be listed for cardiac transplant, United Network for Organ Sharing status 1A, or equivalent 6. Written consent of parent(s) or legally authorized representative (LAR) where appropriate.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- RYAN R DAVIES
NIH-NATIONAL HEART, LUNG AND BLOOD INST
The purpose of this study is to evaluate the feasibility of the investigational Jarvik 2015 ventricular assist device (VaD) for durable left ventricular circulatory support in children. Feasibility will be assessed by evaluating the safety of the Jarvik 2015 device in two cohorts of 5 subjects (5 subjects with standard cardiac anatomy, 5 with challenging cardiac anatomy) as a bridge-to-heart transplantation. The results of the feasibility study will be used to inform the design of the pivotal trial to support FDa approval of the Jarvik 2015 under the Humanitarian Device exemption (HDe) regulation. STuDY HYPoTHeSiS The feasibility of each Jarvik 2015 implant will be evaluated in the context of two categories of cardiac anatomy: Standard Cardiac anatomy: Survival to transplant, recovery or 30 days of device support in the absence of [Greater Than]2 out of 5 device-related neurological compromise events or deaths, or [Greater Than]1 non-oP device failures. Challenging Cardiac anatomy: Survival to transplant, recovery or 10 days of device support in the absence of [Greater Than]2 out of 5 device-related neurological compromise events or deaths, or [Greater Than]1 non-oP device failures. STuDY oBJeCTiVeS anD enDPoinTS Primary objectives Clinical Feasibility To assess the clinical feasibility of the investigational Jarvik 2015 VaD by evaluating survival in the absence of device-related severe neurological impairment or death, or non-operational (non-oP) device failure up to the Clinical endpoint defined as: transplant, recovery or 30 days of support (Standard Cardiac anatomy patients) or 10 days of support (Challenging Cardiac anatomy patients) Safety To evaluate the PeDiMaCS defined serious adverse events (Saes) on Jarvik support up to the Clinical endpoint. Technical, Surgical and Clinical Feasibility To describe the technical, surgical, and clinical feasibility by achieving certain technical, surgical, and clinical milestones that typically accompany a successful VaD support run (see appendix H). evaluation of endpoints To evaluate patients with respect to exploratory primary and secondary endpoints to inform the choice of appropriate primary and secondary endpoints for the pivotal trial. Primary endpoints Clinical Feasibility overall patient survival to the Clinical endpoint as defined by the specific cohorts (Standard Cardiac anatomy vs. Challenging Cardiac anatomy) in Section 4.1.1. -Transplant is defined as induction of anesthesia for cardiac transplant surgery - Recovery is defined as removal of Jarvik 2015 VaD and alive at 12 months post-explant - Severe neurological impairment is defined as PeDiMaCS-defined neurological dysfunction that is associated with severe impairment (i.e. quadriplegia, loss of receptive and expressing language capability, coma) as measured by the Pediatric Stroke outcome Measure neurological exam (PSoM-ne). The PSoM-ne is a standardized, validated neurologic exam for children all ages performed by a pediatric neurologist. The timing of the neurologic assessment to be used and conditions under which it is obtained for calculation of the primary endpoint is described in Section 5.2.2. Device failure is defined as Jarvik 2015 VaD removal (surgical explanation) because of inadequate circulatory support or refractory adverse events that are treated with implantation of a different VaD or eCMo device will be categorized as a failure of the Jarvik 2015 VaD for the purposes of the trial. The addition of an oxygenator alone does not qualify as an eCMo device. Safety PediMaCS-defined (version 5)16 Saes will be reported for each implanted patient along with relationship to the investigational device and implant procedure. Technical, Surgical and Clinical Feasibility Proportion of technical, surgical, and clinical feasibility milestones that typically accompany a successful VaD support run (see appendix H). Please refer to Section 2.3 of the Protocol for the rationale for performing the study.