Pumps for Kids, Infants, and Neonates

Study Overview
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Brief Summary
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PumpKIN is a multicenter, prospective, single-arm feasibility study; Evaluating the investigational Jarvik 2015 VAD in pediatric patients with heart failure. This feasibility trial will enroll 10 subjects at up to 7 sites in the US. The primary objectives of this investigational device exemption (IDE) clinical investigation are to assess the feasibility of using the Jarvik 2015 in pediatric patients with severe heart failure who require mechanical circulatory support. Feasibility will be assessed by evaluating the safety profile of the Jarvik 2015 device in eligible subjects.

Official Title
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Pumps for Kids, Infants, and Neonates

Conditions
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Pediatric Heart Failure

Intervention / Treatment
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* Device: Surgical placement of the Jarvik 2015 VAD
* Procedure: Surgical Placement of Jarvik 2015 VAD


Participation Criteria
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Eligibility Criteria
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Children must meet all of the following criteria: Males and females within weight range 8 to 30 kg Body surface area (BSA) 0.4 m2 to 1.0 m2 Cardiac Diagnosis: 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) INTERMACS Profile 1 or 2 as evidenced by one or more of the following: Inability to wean from extra-corporeal membrane oxygenation (ECMO) or other temporary circulatory support (TCS), OR Inability to wean from mechanical ventilator support, OR 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 ULN for age iii. Alanine 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 difference of >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 d. Inability to ambulate freely to participate fully in age-appropriate activities of daily living (ADLs) and/or cardiac rehabilitation/physical therapy LVAD support is intended for bridge-to transplant. Subject is listed for transplant or eligible (i.e., no medical or surgical contraindications) to be listed for cardiac transplant, United Network for Organ Sharing (UNOS) status 1A, or equivalent Written consent of parent(s) or legally authorized representative (LAR) where appropriate. Children must not meet any of the following exclusion criteria within 48 hours prior to device implant: Known contraindication for systemic anticoagulation Currently participating in an interventional trial whose protocol prevents effective application of Jarvik 2015, potentially has an independent effect on trial endpoints, or otherwise interferes with execution of the PumpKIN protocol Stable inotrope dependence (INTERMACS profile 3) Single ventricle anatomy Presence of a mechanical heart valve Unresolved malignancy CPR with duration >30 consecutive minutes within 48 hours prior to device implant or CPR with uncertain neurological status prior to device implant Renal dysfunction that is severe or, in the opinion of the investigator, irreversible Hepatic dysfunction that is severe or, in the opinion of the investigator, irreversible Severe or irreversible pulmonary dysfunction ECMO use for >10 consecutive days Unrepairable severe aortic insufficiency Active, systemic infection unresponsive to antimicrobial therapy Known cerebrovascular event within the past 30 days or uncertain neurological status Severe right ventricular (RV) dysfunction or significant arrhythmia requiring treatment with an RV assist device (RVAD) (i.e., biventricular assist device) Unmanageable bleeding per judgment of the investigator Ventricular dysfunction that is likely to recover (e.g. myocarditis, metabolic myopathy where LV dysfunction is present solely with intermittent acidosis/crises). Left ventricular end-diastolic dimension or left ventricular end-diastolic volume z score of < +2.5 end-diastolic dimension or ventricular end-diastolic volume z score of < +3.0 Left ventricular ejection fraction of >35%
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Jarvik 2015
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Jarvik 2015 Device VAD<br>New, experimental continuous flow VAD | Device: Surgical placement of the Jarvik 2015 VAD<br>* The Jarvik 2015 VAD is a miniaturized, fully implantable, continuous flow left ventricular assist device.<br>Procedure: Surgical Placement of Jarvik 2015 VAD<br>* Surgical Implant of the Jarvik 2015 VAD is a miniaturized, fully implantable, continuous flow left ventricular assist device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Feasibility | To assess the clinical feasibility of the investigational Jarvik 2015 VAD by evaluating survival in the absence of severe neurological impairment or death, or device failure up to the clinical endpoint defined as transplant, recovery or 30 days of support | 30 days or transplant/recovery (whichever comes first) | 
| Adverse Events | To evaluate the protocol defined (INTERMACS version 5.0) serious adverse events on Jarvik 2015 support up to transplant, recovery or 30 days of support | 30 days or transplant/recovery (whichever comes first) | 
| Technical, surgical, and clinical milestones assessed by feasibility milestones | To describe the technical, surgical and clinical feasibility by achieving specific technical, surgical, and clinical milestones that typically accompany a successful VAD support run | up to 180 days or transplant/recovery | 
| Pivotal Trial continuation assessed by exploratory primary and secondary 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. | 12-months post-explant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events per patient days of VAD support | The incidence rate of protocol-defined AEs (INTERMACS, version 5) per patient-day of VAD support up to the first 180 days post-implant. | 180 days post-implant | 
| Incidence of Adverse Events related to device | Incidence rate of protocol-defined AEs possibly, probably, or definitely related to the device per day of mechanical circulatory support, up to the first 180 days post-implant. | 180 days post-implant | 
| Neurological dysfunction | The incidence of new neurological dysfunction up to 180 days post-implant. | 180 days post-implant | 
| Pediatric Stroke Outcome Measure Neurological Exam (PSOM-NE) score (0 - 10 scale, higher = worse outcome) | Pediatric Stroke Outcome Measure-Neurological (PSOM-NE) score measured at 180 days post-implant or immediately prior to explant, and at 12 months post-explant. | 180 days and 12 months post-explant | 
| King's Outcome Scale for Childhood Head Injury score (0 -5 scale, higher = worse outcome) | King's Outcome Scale for Childhood Head Injury (KOSCHI) score measured at 180 days post-implant or immediately prior to explant, and at 12 months post-explant. | 180 days and 12 months post-explant | 
| Pediatric Stroke Recurrence and Recovery Questionnaire score (0 -10 scale, higher = worse outcome) | Pediatric Stroke Recurrence and Recovery Questionnaire (RRQ) measured at 180 days post-implant or immediately prior to explant, and at 12 months post-explant. | 180 days and 12 months post-explant | 
| Vineland Adaptive Behavior Scales score (scoring and scale different by domain) | Vineland Adaptive Behavior Scales (VABS II) measured at 12 months post-explant. | 12 months post-explant | 
| Pediatric Quality of Life score (0-4 scale per domain, higher = worse outcome) | PedsQL20 measured at 180 days post-implant or immediately prior to explant and 12 months post-explant. | 12 months post-explant | 
| Ventricular Assist Device Quality of Life score (scoring and scale different per question) | VAD QL measured at 30 and 90 days post-implant, and every 90 days thereafter, while on Jarvik 2015 VAD support. | 30 days, 90 days, 12 months post-explant | 
| Paralytics discontinuation | Time to discontinuation of paralytics | 12 months post-explant | 
| TPN discontinuation | Time to discontinuation of total parenteral nutrition (TPN) | 12 months post-explant | 
| Extubation | Time to extubation | 30 days post-implant | 
| Inotropic agents | Time to discontinuation of inotropic agents | 12 months post-explant | 
| Sedation | Time to discontinuation of sedation such that subject is alert and interactive (e.g., engaging in age-appropriate play). | 30 days post-implant | 
| MRI | Brain Magnetic Resonance Imaging (MRI) performed 12 months post-explant to assess for clinically silent neurologic injuries. | 12 months post-explant | 
| Survival in absence of severe neurological impairment | Overall survival in the absence of a severe neurologic impairment and in the absence of device failure at 180 days following VAD implant and meeting any of the following outcomes: Survival to induction of anesthesia for cardiac transplant surgery, Recovery (removal of VAD and alive at 30 days post-explant), Survival at 180 consecutive days of VAD support | 180 days or tranplant/recovery (whichever comes first) | 
| Overall survival in the absence of device failure | Overall survival in the absence of device failure but without regard for neurologic status, meeting any of the following outcomes: Survival to induction of anesthesia for cardiac transplant surgery, Survival to recovery (removal of Jarvik 2015 VAD and alive at 30 days post-explant), Survival at 180 consecutive days of Jarvik 2015 VAD support | 180 days or tranplant/recovery (whichever comes first) | 
| Survival at 30 days post-implant | Survival at 30 days post-implant | 30 days post-implant | 
| Survival at 180 days post-implant | Survival at 180 days post-implant | 180 days post-implant | 
| Survival at 12 months post-explant | Survival at 12 months post-explant | 12 months post-explant | 
| Time to pump failure | Time to first pump failure | device explant | 
| Incidence rate of pump failure | Incidence rate of pump failures | device explant | 
| Time to first pump exchange | Time to first pump exchanges | device explant | 
| Incidence rate of pump exchange | Incidence rate of pump exchanges | device explant | 
| Creatinine level | Proportion of subjects with a creatinine level below the ULNULN | 180 days or immediately prior to explant | 
| ALT level | Proportion of subjects with an alanine aminotransferase (ALT) level below the ULNULN | 180 days or immediately prior to explant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ventricular assist device, congenital heart disease, heart failure