Pumps for Kids, Infants, and Neonates (PumpKIN)

• ClinicalTrials.gov Identifier: NCT02954497
• Recruitment Status: Recruiting
• First Posted: November 3, 2016
• Last Update Posted: January 11, 2021
• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Jarvik Heart, Inc.
• Information provided by (Responsible Party): HealthCore-NERI

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pediatric Heart Failure	Device: Surgical placement of the Jarvik 2015 VAD; Procedure: Surgical Placement of Jarvik 2015 VAD	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Pumps for Kids, Infants, and Neonates
• Actual Study Start Date: October 22, 2018
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: November 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Clinical Feasibility [ Time Frame: 30 days or transplant/recovery (whichever comes first) ]
   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
2. Adverse Events [ Time Frame: 30 days or transplant/recovery (whichever comes first) ]
   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
3. Technical, surgical, and clinical milestones assessed by feasibility milestones [ Time Frame: up to 180 days or transplant/recovery ]
   To describe the technical, surgical and clinical feasibility by achieving specific technical, surgical, and clinical milestones that typically accompany a successful VAD support run
4. Pivotal Trial continuation assessed by exploratory primary and secondary endpoints [ Time Frame: 12-months post-explant ]
   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.

Secondary Outcome Measures :

1. Incidence of Adverse Events per patient days of VAD support [ Time Frame: 180 days post-implant ]
   The incidence rate of protocol-defined AEs (INTERMACS, version 5) per patient-day of VAD support up to the first 180 days post-implant.
2. Incidence of Adverse Events related to device [ Time Frame: 180 days post-implant ]
   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.
3. Neurological dysfunction [ Time Frame: 180 days post-implant ]
   The incidence of new neurological dysfunction up to 180 days post-implant.
4. Pediatric Stroke Outcome Measure Neurological Exam (PSOM-NE) score (0 - 10 scale, higher = worse outcome) [ Time Frame: 180 days and 12 months post-explant ]
   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.
5. King's Outcome Scale for Childhood Head Injury score (0 -5 scale, higher = worse outcome) [ Time Frame: 180 days and 12 months post-explant ]
   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.
6. Pediatric Stroke Recurrence and Recovery Questionnaire score (0 -10 scale, higher = worse outcome) [ Time Frame: 180 days and 12 months post-explant ]
   Pediatric Stroke Recurrence and Recovery Questionnaire (RRQ) measured at 180 days post-implant or immediately prior to explant, and at 12 months post-explant.
7. Vineland Adaptive Behavior Scales score (scoring and scale different by domain) [ Time Frame: 12 months post-explant ]
   Vineland Adaptive Behavior Scales (VABS II) measured at 12 months post-explant.
8. Pediatric Quality of Life score (0-4 scale per domain, higher = worse outcome) [ Time Frame: 12 months post-explant ]
   PedsQL20 measured at 180 days post-implant or immediately prior to explant and 12 months post-explant.
9. Ventricular Assist Device Quality of Life score (scoring and scale different per question) [ Time Frame: 30 days, 90 days, 12 months post-explant ]
   VAD QL measured at 30 and 90 days post-implant, and every 90 days thereafter, while on Jarvik 2015 VAD support.
10. Paralytics discontinuation [ Time Frame: 12 months post-explant ]
    Time to discontinuation of paralytics
11. TPN discontinuation [ Time Frame: 12 months post-explant ]
    Time to discontinuation of total parenteral nutrition (TPN)
12. Extubation [ Time Frame: 30 days post-implant ]
    Time to extubation
13. Inotropic agents [ Time Frame: 12 months post-explant ]
    Time to discontinuation of inotropic agents
14. Sedation [ Time Frame: 30 days post-implant ]
    Time to discontinuation of sedation such that subject is alert and interactive (e.g., engaging in age-appropriate play).
15. MRI [ Time Frame: 12 months post-explant ]
    Brain Magnetic Resonance Imaging (MRI) performed 12 months post-explant to assess for clinically silent neurologic injuries.
16. Survival in absence of severe neurological impairment [ Time Frame: 180 days or tranplant/recovery (whichever comes first) ]
    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
17. Overall survival in the absence of device failure [ Time Frame: 180 days or tranplant/recovery (whichever comes first) ]
    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
18. Survival at 30 days post-implant [ Time Frame: 30 days post-implant ]
    Survival at 30 days post-implant
19. Survival at 180 days post-implant [ Time Frame: 180 days post-implant ]
    Survival at 180 days post-implant
20. Survival at 12 months post-explant [ Time Frame: 12 months post-explant ]
    Survival at 12 months post-explant
21. Time to pump failure [ Time Frame: device explant ]
    Time to first pump failure
22. Incidence rate of pump failure [ Time Frame: device explant ]
    Incidence rate of pump failures
23. Time to first pump exchange [ Time Frame: device explant ]
    Time to first pump exchanges
24. Incidence rate of pump exchange [ Time Frame: device explant ]
    Incidence rate of pump exchanges
25. Creatinine level [ Time Frame: 180 days or immediately prior to explant ]
    Proportion of subjects with a creatinine level below the ULNULN
26. ALT level [ Time Frame: 180 days or immediately prior to explant ]
    Proportion of subjects with an alanine aminotransferase (ALT) level below the ULNULN

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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%

Contacts and Locations

Contacts

Contact: Ashley Magnavita, MPH; 6179723182 ext 6179723182; amagnavita@healthcore.com

Locations

United States, California

Lucile Packard Children's Hospital Stanford; Recruiting

Palo Alto, California, United States, 94304

Contact: David Rosenthal, MD davidnr@stanford.edu

United States, Georgia

Children's Healthcare of Atlanta; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Kirk Kanter, MD 404-785-6330 kkanter@emory.edu

United States, Massachusetts

Boston Children's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Francis Flynn-Thompson, MD Francis.Fynn-Thompson@cardio.chboston.org

United States, New York

Columbia University Medical Center; Recruiting

New York, New York, United States, 10032

Contact: Paul Chai, MD 212-305-5975 pjc@cumc.columbia.edu

United States, Ohio

Cincinnati Children's Hospital Medical Center; Recruiting

Cincinnati, Ohio, United States, 45229

Contact: David Morales, MD david.morales@cchmc.org

United States, Texas

Children's Medical Center - Dallas; Recruiting

Dallas, Texas, United States, 75235

Contact: Ryan Davies, MD 214-456-5000 ryan.davies@utshouthwestern.edu

Texas Children's Hospital; Recruiting

Houston, Texas, United States, 77030

Contact: Iki Adachi, MD ixadachi@texaschildrens.org

Sponsors and Collaborators

HealthCore-NERI

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

More Information

• Responsible Party: HealthCore-NERI
• ClinicalTrials.gov Identifier: NCT02954497
• Other Study ID Numbers: C01367
• First Posted: November 3, 2016
• Last Update Posted: January 11, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Limited use data set will be made available through NHLBI after the conclusion of the trial.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by HealthCore-NERI:

ventricular assist device; congenital heart disease; heart failure

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases