NCT01005316

Alloantibodies in Pediatric Heart Transplantation

• Status: Terminated
• Phase: —
• Study type: Observational
• Enrollment: 290 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients.

Detailed description

There is currently a renewed interest in alloantibodies in transplantation. In 1966, Kissmeyer and colleagues reported that pre-existing antibodies directed against donor cells could cause hyperacute rejection of the renal allograft. Three years later, in a landmark study, Patel and Terasaki showed that a lymphocytotoxic assay to identify donor-specific antibodies was highly predictive of acute graft failure. These observations led to the practice of performing prospective, donor-specific crossmatches by lymphocytotoxicity assay for all kidney transplants and for heart and lung transplants when the candidate has a positive panel reactive antibody (PRA) assay. A concept evolved that transplantations should not be performed across a positive cytotoxicity crossmatch. The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients. This study plans to enroll 370 pediatric heart transplant recipients over a period of 3 years. The follow-up period will last up to 3 years. All participants will be enrolled pretransplant. In the pretransplant phase, visits will occur every 6 months. These routine visits will continue until transplant or the end of the study. They will coincide with routine pretransplant status visits. At the time of transplant, the participants will be assigned to one of two groups. Group A will include participants who are allo-antibody negative (less than 10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Cohort B will include participants who have the presence of a DTT-treated AHG CDC-PRA of greater than or equal to 10% and/or an ELISA-PRA greater than or equal to 10% in any pretransplant sample. Both cohorts will receive standard transplantation care. This study has no interventions. All participants will undergo regular blood tests, and, those in the sensitized group will have additional blood testing performed after the transplant and lasting until the end of the study. Post-transplant visits will occur while participants are recovering in the hospital; at Months 1, 3, and 6; and annually until the study closes. The information collected for the study include data from a physical exam, routine testing, adverse (AEs) and serious adverse (SAEs) events assessments, and blood collection. Each time a biopsy is done, the study will ask to review the biopsy tissue and to collect a sample. If stored tissue is not available, none will be collected.

Conditions

• Pediatric Heart Transplantation
• Pediatric Heart Transplant Recipients

Interventions

Type	Name	Description
DRUG	Induction Therapy	Per standard of care guidelines for immunosuppression at each clinical site.
DRUG	Tacrolimus	Per standard of care guidelines for immunosuppression at each clinical site.
DRUG	Mycophenolate Mofetil	Per standard of care guidelines for immunosuppression at each clinical site.
PROCEDURE	Intraoperative plasma exchange/pheresis	Per standard of care guidelines for immunosuppression at each clinical site.
PROCEDURE	Short-term post-operative plasmapheresis	Per standard of care guidelines for immunosuppression at each clinical site.
DRUG	Immunoglobulins, Intravenous	Post-transplant course of intravenous immunoglobulin therapy per standard of care guidelines for immunosuppression at each clinical site.
DRUG	Prednisone	Maintenance corticosteroids per standard of care guidelines for immunosuppression at each clinical site.

Timeline

• Start date: 2010-01-01
• Primary completion: 2014-12-01
• Completion: 2014-12-01
• First posted: 2009-10-30
• Last updated: 2017-04-20
• Results posted: 2017-04-20

Locations

8 sites across 2 countries: United States, Canada