Pumps for Kids, Infants, and Neonates (PumpKIN)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pediatric Heart Failure
• Intervention / Treatment: Device: Surgical placement of the Jarvik 2015 VAD; Procedure: Surgical Placement of Jarvik 2015 VAD

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital Stanford
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center - Dallas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Children must meet all of the following criteria:

1. Males and females within weight range 8 to 30 kg
2. Body surface area (BSA) 0.4 m2 to 1.0 m2

3. 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)

4. INTERMACS Profile 1 or 2 as evidenced by one or more of the following:

   1. Inability to wean from extra-corporeal membrane oxygenation (ECMO) or other temporary circulatory support (TCS), OR
   2. Inability to wean from mechanical ventilator support, OR
   3. 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

5. 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
6. 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:

1. Known contraindication for systemic anticoagulation
2. 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
3. Stable inotrope dependence (INTERMACS profile 3)
4. Single ventricle anatomy
5. Presence of a mechanical heart valve
6. Unresolved malignancy
7. CPR with duration >30 consecutive minutes within 48 hours prior to device implant or CPR with uncertain neurological status prior to device implant
8. Renal dysfunction that is severe or, in the opinion of the investigator, irreversible
9. Hepatic dysfunction that is severe or, in the opinion of the investigator, irreversible
10. Severe or irreversible pulmonary dysfunction
11. ECMO use for >10 consecutive days
12. Unrepairable severe aortic insufficiency
13. Active, systemic infection unresponsive to antimicrobial therapy
14. Known cerebrovascular event within the past 30 days or uncertain neurological status
15. Severe right ventricular (RV) dysfunction or significant arrhythmia requiring treatment with an RV assist device (RVAD) (i.e., biventricular assist device)
16. Unmanageable bleeding per judgment of the investigator
17. Ventricular dysfunction that is likely to recover (e.g. myocarditis, metabolic myopathy where LV dysfunction is present solely with intermittent acidosis/crises).
18. 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
19. Left ventricular ejection fraction of >35%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Carelon Research
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Jarvik Heart, Inc.
• Investigators: Study Chair: William T Mahle, MD, Children's Hospital of Atlanta, Emory University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2018
• Primary Completion (Actual): June 9, 2023
• Study Completion (Estimated): September 15, 2023

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimated): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: heart failure; congenital heart disease; ventricular assist device
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: C01367

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Limited use data set will be made available through NHLBI after the conclusion of the trial.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes