EXCOR® Pediatric VAD Anticoagulation IDE

EXCOR® Pediatric VAD Anticoagulation IDE Investigational Plan

The Berlin Heart EXCOR ventricular assist device received approval from the FDA as a bridge to transplantation for children in 2011. Successful bridge to transplantation or recovery in the IDE trial of the Berlin Heart EXCOR was 88% to 92%, but a high incidence of neurological injury was reported in this trial (29%).

Stroke remains the most important complication of Berlin Heart EXCOR support, with high mortality rates, and considerable long-term morbidity. The EXCOR IDE study incorporated a novel anticoagulation protocol (henceforth referred to as the Edmonton Anticoagulation Protocol). The preponderance of ischemic strokes in this study raised the question of whether the anticoagulation protocol was sufficiently intensive, as ischemic strokes in this setting are virtually always thromboembolic phenomena. In response to these data and to the experience at the investigator's institution, a novel anticoagulation protocol has been devised for use with the EXCOR (Stanford anticoagulation protocol).The purpose of this study is to perform a pilot evaluation of this protocol in a multi--center setting, to prepare for a randomized trial between this and a subsequent iteration of anticoagulation treatment.

Study Overview

• Status: Withdrawn
• Conditions: Pediatric HD
• Intervention / Treatment: Device: novel anticoagulation protocol used in conjunction with the Berlin Heart EXCOR

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Severe heart failure (NYHA functional class IV, or Ross functional class IV if < age 6 years of age), refractory to optimal medical therapy
2. Patient deemed to be candidate for EXCOR implantation according to the clinical criteria employed by treating site
3. Listed or eligible for cardiac transplantation according to the criteria employed by the treating site
4. Two-ventricle circulation, including cardiomyopathy, repaired structural heart disease, or acquired heart disease
5. Age 0 to 18 years of age
6. Corrected gestational age ≥ 37 weeks
7. Weight ≥ 3 kg and ≤ 60 kg

8. Legal guardian (and patient if age-appropriate) understands the nature of the investigation, is willing to comply with the protocol and associated evaluations, and provides written informed consent and assent prior to the procedure.

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Exclusion Criteria:

1. Support on ECMO for ≥10 days
2. Cardiopulmonary resuscitation (CPR) duration ≥ 30 minutes within 48 hours prior to device implantation
3. Body weight < 3.0 kg or BSA > 1.5 m2
4. Presence of mechanical aortic valve
5. Unfavorable or technically-challenging cardiac anatomy including single ventricle lesions, complex heterotaxy, and restrictive cardiomyopathy.
6. Evidence of intrinsic hepatic disease as defined by a total bilirubin level or ALT greater than 5 times the upper limit of normal for age, except in association with acute heart failure as determined by the site principal investigator
7. Evidence of intrinsic renal disease as defined by a serum creatinine greater than 3 times the upper limit of normal for age, except in association with acute heart failure as determined by the investigator
8. Hemodialysis or peritoneal dialysis (not including dialysis or continuous veno-venous hemofiltration (CVVH) for volume removal)
9. Evidence of intrinsic pulmonary disease (eg chronic lung disease, or ARDS) as defined by need for positive pressure ventilation, except in association with acute heart failure as determined by the principal investigator
10. Moderate or severe aortic and/or pulmonary valve insufficiency considered technically challenging to repair at the time of the device implantation as determined by the principal investigator
11. Apical VSD or other hemodynamically-significant lesion considered technically challenging to repair at the time of device implantation as determined by the principal investigator
12. Documented heparin induced thrombocytopenia (HIT) or idiopathic thrombocytopenia purpura (ITP) or other contraindication to anticoagulant/antiplatelet therapy
13. Documented coagulopathy (e.g. Factor VIII deficiency, disseminated intravascular coagulation) or thrombophilic disorder (e.g. Factor V Leiden mutation)
14. Hematologic disorder causing fragility of blood cells or hemolysis (e.g. sickle cell disease)
15. Platelets < 70,000/ml within 24 hours prior to device implantation
16. Active infection within 48 hours of implant (positive blood culture OR temperature > 38 degrees C AND wbc > 15,000/ml)
17. Documented human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
18. Evidence of recent or life-limiting malignant disease
19. Stroke within past 30 days prior to enrollment, or congenital CNS malformation syndrome associated with increased risk of bleeding (e.g. arteriovenous malformation, moya moya)
20. Psychiatric or behavioral disease (e.g. antisocial disorder) with a high likelihood for non-adherence to the protocol and follow-up
21. Currently participating in another investigational device or drug trial and has not completed the required follow-up period for that study. EXCEPTION: Dual enrollment in PUMPKIN study is permitted.

22. Patient is pregnant or nursing

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• 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: single-arm novel anticoagulation; Single-arm clinical study to assess the safety, and effectiveness of a novel anticoagulation protocol to be used in conjunction with the Berlin Heart EXCOR Pediatric Ventricular Assist Device as a bridge to heart transplantation in children with severe heart failure who have failed optimal medical therapy.	Device: novel anticoagulation protocol used in conjunction with the Berlin Heart EXCOR; novel antithrombotic management protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of major bleeding adverse events reported using the Stanford Anti-Thrombotic Protocol.	To test the safety of the Stanford Anti-Thrombotic Protocol.	Up to 90 days
Number of all forms of stroke events reported using the Stanford Anti-Thrombotic Protocol.	To test the effectiveness of the Stanford Anti-Thrombotic protocol.	Up 90 days

Collaborators and Investigators

• Sponsor: David N. Rosenthal

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Actual): January 17, 2019

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: heart failure
• Other Study ID Numbers: IRB-47736

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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