Alloantibodies in Pediatric Heart Transplantation

National Institute of Allergy and Infectious Diseases (NIAID)

Status: Terminated

Conditions: Pediatric Heart Transplantation; Pediatric Heart Transplant Recipients

Treatments: Drug: Prednisone; Procedure: Short-term post-operative plasmapheresis; Drug: Mycophenolate Mofetil; Procedure: Intraoperative plasma exchange/pheresis; Drug: Tacrolimus; Drug: Induction Therapy; Drug: Immunoglobulins, Intravenous

Study type: Observational

Funder types: NIH

Identifiers

NCT01005316

DAIT CTOTC-04

7U01AI077867-02 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 290 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• All participants listed for heart transplantation at participating CTOT-C study sites.

Exclusion criteria

• Listed for multiple organ transplant
• Inability or unwillingness of the participant or parent/guardian to give written informed consent or comply with the study protocol
• Condition or characteristic which in the opinion of the investigator makes the participant unlikely to complete at least one year of follow-up
• Current participation in other research studies that would, or might, interfere with the scientific integrity or safety of current study (e.g. by interference with immunosuppression management guidelines, study endpoints, excessive blood draws or SAE evaluation).

Trial design

290 participants in 2 patient groups

Cohort A: Non-Sensitized

Description:

Cohort A will include participants who are alloantibody Luminex(TM) LABScreen. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Non-sensitized recipients receive steroid-free maintenance immunosuppression: 1. Induction Therapy (anti-T cell antibody induction) 2. Tacrolimus (Prograf®) 3. Mycophenolate Mofetil- MMF (CellCept®).

Treatment:

Drug: Induction Therapy

Drug: Tacrolimus

Drug: Mycophenolate Mofetil

Cohort B: Sensitized

Description:

Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Sensitized recipients receive: 1. Induction Therapy (anti-T cell antibody induction) 2. Intraoperative plasma exchange/pheresis 3. Short-term post-operative plasmapheresis 4. Post-transplant course of intravenous immunoglobulin (IVIG) therapy 5. Maintenance corticosteroids (Prednisone) 6. Tacrolimus (Prograf®) 7. Mycophenolate Mofetil-MMF (CellCept®).

Treatment:

Drug: Immunoglobulins, Intravenous

Drug: Induction Therapy

Drug: Tacrolimus

Procedure: Intraoperative plasma exchange/pheresis

Drug: Mycophenolate Mofetil

Procedure: Short-term post-operative plasmapheresis

Drug: Prednisone