title: Berlin Heart EXCOR Pediatric ventricular assist device Investigational Device Exemption study: study design and rationale.
abstract: BACKGROUND
  Currently, there are no Food and Drug Administration-approved devices available that can provide long-term mechanical circulatory support to smaller children with severe heart failure as a bridge to heart transplant (HT). In recent years, the Berlin Heart EXCOR Pediatric ventricular assist device (VAD) has emerged as a potential treatment option. Systematic data on the safety and efficacy of the EXCOR are limited.
  
  
  METHODS
  The Investigational Device Exemption (IDE) clinical study is designed to evaluate the safety and probable benefit of the EXCOR to support regulatory review of the device under the Humanitarian Device Exemption regulation. The study design and rationale are reviewed in light of the well-described challenges inherent in small population studies.
  
  
  RESULTS
  The Berlin Heart EXCOR IDE clinical study is a prospective, multicenter, single-arm, clinical cohort study. Children aged 0 to 16 years with severe heart failure (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2) due to 2-ventricle heart disease and actively listed for HT comprise the primary study cohort. The control population is a propensity-matched retrospective cohort of children supported with extracorporeal membrane oxygenation, the only bridge device available to smaller children before the EXCOR. The primary efficacy end point is survival to heart transplantation or recovery. The primary safety end point is the incidence of serious adverse events as defined by pediatric Interagency Registry for Mechanically Assisted Circulatory Support criteria. The study will enroll a total of 48 subjects in 2 cohorts based on body surface area (cohort 1 <0.7 m(2), cohort 2 0.7-1.5 m(2)) and is powered to show safety superiority to a prespecified performance goal of 0.25 serious adverse events per day of support. Children ineligible for the primary cohort will still have access to the device in a third compassionate-use cohort where adverse event data will be collected for additional safety characterization of the device.
  
  
  CONCLUSIONS
  The Berlin Heart IDE clinical study will be the first bridge-to-HT VAD study designed exclusively for children. It is anticipated that the study will provide important information on the safety and efficacy of the Berlin Heart EXCOR Pediatric in children while providing valuable lessons into the design and conduct of future VAD studies in children.
authors: The Cardiology Clinical Research and Regulatory Group, Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. christopher.almond@cardio.hchboston.org
authors: Christopher S
authors: CS
authors: Almond
authors: Holger
authors: H
authors: Buchholz
authors: Patricia
authors: P
authors: Massicotte
authors: Rebecca
authors: R
authors: Ichord
authors: David N
authors: DN
authors: Rosenthal
authors: Karen
authors: K
authors: Uzark
authors: Robert D B
authors: RD
authors: Jaquiss
authors: Robert
authors: R
authors: Kroslowitz
authors: Mary Beth
authors: MB
authors: Kepler
authors: Aaron
authors: A
authors: Lobbestael
authors: David
authors: D
authors: Bellinger
authors: Elizabeth D
authors: ED
authors: Blume
authors: Charles D
authors: CD
authors: Fraser
authors: Robert H
authors: RH
authors: Bartlett
authors: Ravi
authors: R
authors: Thiagarajan
authors: Kathy
authors: K
authors: Jenkins
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011300:Preoperative Care / Q000295:instrumentation*; D011446:Prospective Studies; D020127:Recovery of Function / Q000502:physiology*; D016037:Single-Blind Method; D016896:Treatment Outcome; D016276:Ventricular Function / Q000502:physiology*