Allo-Antibodies in Pediatric Heart Transplantation

Pediatric Heart Transplantation Clinical Trial

Official title:

Allo-Antibodies in Pediatric Heart Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01005316
• Other study ID #: DAIT CTOTC-04
• Secondary ID: U01A1077867 01
• Status: Completed
• Phase: N/A
• First received: October 27, 2009
• Last updated: October 5, 2015
• Start date: January 2010
• Est. completion date: December 2014

Study information

• Verified date: October 2015
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review BoardUnited States: Data and Safety Monitoring Board
• Study type: Observational

Clinical Trial Summary

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

Description:

There is currently a renewed interest in allo-antibodies 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 cross-matches 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 cross-match. The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity cross-match and to compare them with outcomes in nonsensitized heart transplant recipients.

This study will 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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).

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Pediatric Heart Transplant Recipients
• Pediatric Heart Transplantation

Intervention

Drug:
• Induction Therapy
Per standard of care guidelines for immunosuppression at each clinical site.
• Tacrolimus
Per standard of care guidelines for immunosuppression at each clinical site.
• 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.
• 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.
• Prednisone
Maintenance corticosteroids per standard of care guidelines for immunosuppression at each clinical site.

Locations

Country	Name	City	State
Canada	Hospital for Sick Children, Labatt Family Heart Centre	Toronto	Ontario
United States	Children's Hospital Boston, Harvard Medical School	Boston	Massachusetts
United States	Children's Hospital at Montefiore	Bronx	New York
United States	Vanderbilt University	Nashville	Tennessee
United States	Children's Hospital of New York, Columbia University Medical Center	New York	New York
United States	Children's Hospital of Philadelphia, University of Pennsylvania	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	St. Louis Children's Hospital, Washington University	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969 Apr 3;280(14):735-9. — View Citation

Rose ML, Smith JD. Clinical relevance of complement-fixing antibodies in cardiac transplantation. Hum Immunol. 2009 Aug;70(8):605-9. doi: 10.1016/j.humimm.2009.04.016. Epub 2009 Apr 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of the Incidence of Death, Retransplantation or Rejection with Hemodynamic Compromise		At month 12 post-transplantation	Yes
Secondary	Incidence of Allo-Antibody Production Post-Transplantation	Incidence of de novo alloantibody production post-transplantation impact on graft and participant outcomes in cohort A participants.	Study enrollment to end of study	Yes
Secondary	Time to Production of Post-Transplant de novo Allo-Antibodies	This endpoint will help determine the specificity and time course of production of post-transplant de novo allo-antibodies and risk factors for their development in transplant recipients (Cohort A).	Study enrollment to end of study	Yes
Secondary	Incidence of Death While on Transplant Wait-List	Cohort A and Cohort B: Pre-transplant	Study enrollment to time of transplant	Yes
Secondary	Time from Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing	Cohort A and Cohort B: Pre-transplant	Study enrollment to time of transplant	Yes
Secondary	Presence and Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing	Cohort A and Cohort B: Pre-transplant	Study enrollment to time of transplant	Yes
Secondary	Presence of Anti-MICA Antibodies by Luminex TM assay	Cohort A and Cohort B: Pre-transplant	Study enrollment to time of transplant	Yes
Secondary	Overall Participant and Graft Survival	Cohort A and Cohort B: Post-transplant	Time of transplant to end of study	Yes
Secondary	Presence of C4d on Endomyocardial Biopsy (EMB)	Cohort A and Cohort B: Post-transplant	time of transplant to end of study	Yes
Secondary	Incidence of Rehospitalizations	Cohort A and Cohort B: Post-transplant	Time of transplant to end of study	Yes
Secondary	Incidence of Severe Infections	Cohort A and Cohort B: Post-transplant	time of transplant to end of study	Yes
Secondary	Time to Diagnosis of Chronic Rejection (Graft Coronary Artery Disease)	Cohort A and Cohort B: Post-transplant	Time of transplant to end of study	Yes
Secondary	Time to Post-Transplantation Lymphoproliferative Disorder	Cohort A and Cohort B: Post-transplant	Time of transplant to end of study	Yes
Secondary	Time to New-Onset Diabetes Mellitus	Cohort A and Cohort B: Post-transplant	Time of transplant to end of study	Yes
Secondary	Frequency and Time to Acute Rejection	Cohort A and Cohort B: Post-transplant	Time of transplant to end of study	Yes

External Links

•   Clinical Trials in Organ Transplantation in Children (CTOT-C)
•   National Heart Lung and Blood Institute (NHLBI)
•   National Institute of Allergy and Infectious Diseases (NIAID)