Two-Year Study of the Safety and Efficacy of the Second-Generation Tissue Engineered Vascular Grafts

Prospective, Open-labeled, Single-arm Clinical Trial to Evaluate the Safety and Efficacy of the Second-generation Tissue Engineered Vascular Graft as Vascular Conduits for Extracardiac Total Cavopulmonary Connection.

A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary connection.

This investigation is a prospective, open-labeled clinical trial determining the safety of the use of tissue engineered vascular grafts as conduits for EC TCPC. Patients will be monitored for adverse events (AE) and serious adverse events (SAE). Special attention will be paid to the incidence of stenosis. We will determine graft-related morbidity and mortality for the second generation TEVGs which will include any post-operative complication such as any aneurismal dilation, stenosis, thromboembolic or infectious event that requires treatment and is thought to be caused by the graft as determined by the investigators and confirmed by the data safety monitoring board. The graft related complication rates will be compared between the first and second generation TEVGs. An interim analysis will be performed to assess the incidence of early (<6 month) graft-related complications in the first 6 enrolled patients. Safety and tolerability will be assessed through serial imaging, to determine the effect of growth and remodeling on graft performance through echocardiography and 4-dimensional MRI. All appropriate patients requiring EC TCPC who meet study inclusion/exclusion criteria will be evaluated for enrollment in the clinical trial. All enrolled subjects will be required to have follow-up visits at Nationwide Children's Hospital for a minimum of 2 years following implant. After obtaining informed consent for the patient's parents, patients with single ventricle cardiac anomalies will undergo EC TCPC using a tissue engineered conduit. Post-operative care and monitoring will follow an established, standardized, clinical algorithm in which the patient's clinical status including complications and measurements of graft function will be serially evaluated and recorded over a two year period using physical examination, echocardiography, and MRI.

Inclusion Criteria:

• Patients will be eligible for inclusion in the study if they meet all of the following criteria.

  1. Patient must be a candidate to undergo an extracardiac total cavopulmonary connection.
  2. Patient and/or legal guardian must voluntarily provide informed consent/assent for participation in the study.

Exclusion Criteria:

• Patients will be excluded from participation in the study if they meet any of the following criteria.

  1. Patient has an urgent/emergent operative status.
  2. Patient has acute renal failure or renal insufficiency in the opinion of the investigator
  3. Patient requires a graft less than 12 mm or greater than 24 mm in diameter.
  4. Patient has a pacemaker.
  5. Patient has pulmonary vascular resistance greater than 4 um2 (u=Wood's units)
  6. Patient has abnormal venous drainage (interrupted inferior vena cava [IVC]).
  7. Patient presents with significant atrio-ventricular valve regurgitation that in the opinion of the investigator, makes them ineligible.
  8. Patient has a history of another condition or significant medical problem that, in the opinion of the investigator, precludes compliance with protocol-specified procedures.
  9. Patients taking any medications that in the opinion of the Investigator could interfere with the TEVG, including bisphosphonates (i.e. Clodronate or Zoledronate).
  10. Patient or parent/legal guardian is, in the opinion of the investigator, unable to comply with protocol evaluations.
  11. Preoperative hemoglobin <11.0 mg/dL at time of patient's pre-admission testing.