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News from the PumpKIN Patch


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Janet N Scheel, MD
ISHLT Pediatric Transplantation Council Chair
Children's National Health System
Washington, DC
jscheel@childrensnational.org



In February 2010 the National Heart, Lung, and Blood Institute (NHLBI) funded the Pumps for Kids, Infants, and Neonates (PumpKIN) Pre-clinical Program for preclinical testing of mechanical circulatory support devices for infants and children with heart failure. The goal was to support the continued development and necessary FDA testing of promising devices at that time, including some of those from the 2004 NHLBI funded Pediatric Circulatory Support Program. For us in the pediatric community, this was great news. At present, our only option for long term support in our smallest patients is the Berlin Heart EXCOR, initially approved in Europe in 1996, approved in Canada in 2009 and the US in 2011. Prior to approval, it was widely used on a compassionate basis. While the Berlin Heart EXCOR has been a valuable and necessary therapy that has certainly saved many lives, it is paracorporeal and pulsatile. The advantage of intracorporeal, continuous flow devices, such as those developed in the PumpKIN program, has been clearly shown in adults and results in fewer thrombotic complications, increased mobility and the possibility of hospital discharge. It has also been suggested that there is less risk for allosensitization with continuous flow devices. As our waitlist times increase, an intracorporeal pediatric continuous flow device would be a great addition to our growing armamentarium against pediatric heart failure.

This week I had the opportunity to attend The Annual Meeting of the American Society for Artificial Internal Organs here in Washington, D.C. An update on the PumpKIN trial was given by the director of the program, Tim Baldwin, PhD, The Deputy Chief of The Advanced Technologies and Surgery Branch in the Division of Cardiovascular Sciences at NHLBI.

The trial is getting ready to enter its clinical phase. In 2013, the protocol was reviewed by the NHLBI PRC and by the FDA (through a pre-IDE meeting), and clinical sites were selected. The IDE was submitted to the FDA in late April 2014 and an amended IDE, containing additional test results, justifications, and documentation to address FDA's feedback, will be submitted in this July. Central training has begun, starting with a session completed at the Duke Medical Center and another scheduled for the last week of June at Texas Children's Hospital. Initially two advanced compact ECMO devices, the Infant Jarvik 2000, and another continuous flow miniature VAD were funded thought the PumpKIN program. At present the Infant Jarvik 2000 is the only device left as part of the PumpKIN trial. Roughly the length of a paper clip, this device features a new type of miniature blood immersed ceramic bearing called the cone bearing, which has decreased the thrombosis seen with the previously used pin-in-sleeve bearings. Rather than the single arm study matched with ECMO of the Berlin Heart trial, this study will be a two arm prospective randomized trial with patients randomized 1:1 to receive either the Berlin Heart EXCOR or the Infant Jarvik 2000. The goal sample size is a total of 88 patients with 44 receiving each device, an increase from the 24 patient enrolled in the Berlin Heart Study. Patients will need to be 4-15 kgs or have a BSA < 0.6 M2. While the Berlin Heart Study targeted patients 3.6-13.6 kgs or >0.7 M2.

Twenty-two centers will be participating in the trial. The end point of the trial will be survival of anesthesia for transplant, survival at 180 days or survival until explant for recovery as opposed to the Berlin Heart Study where the outcome was death. All enrolled patients must be eligible for transplant. The clinical phase is expected to start later this year and run through 2018 with data analysis beginning the same year.

Challenges have plagued this trial in the past and as it proceeds, it will continue to face a variety of obstacles. With the Berlin Heart now being used in many centers, the Infant Jarvik 2000 will be competing against a device that is FDA approved and has a proven track record. The number of clinical centers participating in the study and submitting data will present its own challenges. In addition, the limited patient population requires the participation of a larger number of centers than the original 22 involved if the target enrollment is to become a reality.

Despite these obstacles, it remains very important for the field of pediatric heart failure that the trial move forward. The portability and risk profile of continuous flow devices have become clearly preferable to paracorpeal pulsatile devices for use in adults and larger children. As our use of devices grows, so does our transplant list and waiting times. Our patients' quality of life would be significantly improved if they could wait in the comfort of their own home. It is also within the realm of possibilities that the future generation of devices will have better survival curves than those of transplantation. As a pediatric community, we are very anxious to see what we will learn from the PumpKIN trial—we just wish we did not have to wait so long.... ■

Special Thanks to Tim Baldwin PhD for his help with this article.

Disclosure Statement: the author has no conflicts of interest to disclose.


References:

  1. Fraser CD, Jr, Jaquiss RD, Rosenthal DN, et al: Prospective trial of a pediatric ventricular assist device. N Engl J Med 367: 532-42, 2012
  2. Starling RC, Naka Y, Boyle AJ, et al: Results of the post U.S. Food and Drug Administration-approval study with continuous flow left ventricular assist devices as a bridge to heart transplantation: A prospective study using the INTERMACS. J Am Coll Cardiol 57:1890-1898, 2011



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