Clinical trial NCT01005316: Alloantibodies in Pediatric Heart Transplantation
Official title: Alloantibodies in Pediatric Heart Transplantation
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Pediatric Heart Transplantation
Pediatric Heart Transplant Recipients
Keywords: cohort study
allo-antibodies
allosensitization
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-10-30
Enrollment: 290
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric heart transplantation candidates

Brief 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation
timeFrame: 12 months post-transplantation
Secondary outcomes:
measure: Time to Production of Post-Transplant de Novo Donor-specific Alloantibodies
timeFrame: Transplantation to first year post transplant (up to 12 months post transplant).
measure: Percentage of Participants Positive for de Novo Donor-Specific Alloantibody Production in the First Year Post-Transplantation
timeFrame: Transplantation to first year post transplant (up to 12 months post transplant).
measure: Percentage of Participants- Mortality While on Transplantation Wait-List
timeFrame: Pre-transplantation
measure: Time From Participant Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing
timeFrame: Study enrollment to transplantation
measure: Percentage of Participants With the Presence of Anti-HLA IgG Antibodies by Luminex SA Testing
timeFrame: Pre-transplantation
measure: Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing
timeFrame: Pre-transplantation
measure: Percentage of Participants With the Presence of Anti-MICA Antibodies by Luminex TM Assay
timeFrame: Pre-Transplantation
measure: Percentage of Participants -Overall Participant and Graft Survival
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Presence of C4d on Endomyocardial Biopsy (EMB)
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Percentage of Participants With Occurrence of Re-Hospitalization(s)
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Percentage of Participants Positive for Severe Infection(s)
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Time to Diagnosis of Chronic Rejection
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Time to Post-Transplantation Lymphoproliferative Disorder
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Time to New-Onset Diabetes Mellitus
timeFrame: Transplantation to the end of study (up to 4 years post transplant).
measure: Percentage of Participants Experiencing Acute Rejection
timeFrame: Transplantation to the end of study.
measure: Time to Acute Rejection
timeFrame: Transplantation to the end of study.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston, Harvard Medical School
state: Massachusetts
city: St. Louis
country: United States
facility: St. Louis Children's Hospital, Washington University
state: Missouri
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: New York
country: United States
facility: Children's Hospital of New York, Columbia University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia, University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Toronto
country: Canada
facility: Hospital for Sick Children, Labatt Family Heart Centre
state: Ontario
Study officials:
affiliation: University of Pittsburgh
name: Stephen A. Webber, MBChB, MRCP
role: STUDY_CHAIR
References:
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.
citation: Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969 Apr 3;280(14):735-9. doi: 10.1056/NEJM196904032801401. No abstract available.
citation: Lamour JM, Mason KL, Hsu DT, Feingold B, Blume ED, Canter CE, Dipchand AI, Shaddy RE, Mahle WT, Zuckerman WA, Bentlejewski C, Armstrong BD, Morrison Y, Diop H, Ikle DN, Odim J, Zeevi A, Webber SA; CTOTC-04 investigators. Early outcomes for low-risk pediatric heart transplant recipients and steroid avoidance: A multicenter cohort study (Clinical Trials in Organ Transplantation in Children - CTOTC-04). J Heart Lung Transplant. 2019 Sep;38(9):972-981. doi: 10.1016/j.healun.2019.06.006. Epub 2019 Jun 20.