Alloantibodies in Pediatric Heart Transplantation

NCT ID: NCT01005316

Last Updated: 2017-04-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

290 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-01-31

Study Completion Date

2014-12-31

Brief Summary

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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

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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

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Pediatric Heart Transplantation Pediatric Heart Transplant Recipients

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort A: Non-Sensitized

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®).

Induction Therapy

Intervention Type DRUG

Per standard of care guidelines for immunosuppression at each clinical site.

Tacrolimus

Intervention Type DRUG

Per standard of care guidelines for immunosuppression at each clinical site.

Mycophenolate Mofetil

Intervention Type DRUG

Per standard of care guidelines for immunosuppression at each clinical site.

Cohort B: Sensitized

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®).

Induction Therapy

Intervention Type DRUG

Per standard of care guidelines for immunosuppression at each clinical site.

Tacrolimus

Intervention Type DRUG

Per standard of care guidelines for immunosuppression at each clinical site.

Mycophenolate Mofetil

Intervention Type DRUG

Per standard of care guidelines for immunosuppression at each clinical site.

Intraoperative plasma exchange/pheresis

Intervention Type PROCEDURE

Per standard of care guidelines for immunosuppression at each clinical site.

Short-term post-operative plasmapheresis

Intervention Type PROCEDURE

Per standard of care guidelines for immunosuppression at each clinical site.

Immunoglobulins, Intravenous

Intervention Type DRUG

Post-transplant course of intravenous immunoglobulin therapy per standard of care guidelines for immunosuppression at each clinical site.

Prednisone

Intervention Type DRUG

Maintenance corticosteroids per standard of care guidelines for immunosuppression at each clinical site.

Interventions

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Induction Therapy

Per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type DRUG

Tacrolimus

Per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type DRUG

Mycophenolate Mofetil

Per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type DRUG

Intraoperative plasma exchange/pheresis

Per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type PROCEDURE

Short-term post-operative plasmapheresis

Per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type PROCEDURE

Immunoglobulins, Intravenous

Post-transplant course of intravenous immunoglobulin therapy per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type DRUG

Prednisone

Maintenance corticosteroids per standard of care guidelines for immunosuppression at each clinical site.

Intervention Type DRUG

Other Intervention Names

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anti-T cell antibody induction Prograf® CellCept® MMF plasmapheresis pheresis IVIG corticosteroid

Eligibility Criteria

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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).
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen A. Webber, MBChB, MRCP

Role: STUDY_CHAIR

University of Pittsburgh

Locations

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Children's Hospital Boston, Harvard Medical School

Boston, Massachusetts, United States

Site Status

St. Louis Children's Hospital, Washington University

St Louis, Missouri, United States

Site Status

Children's Hospital of New York, Columbia University Medical Center

New York, New York, United States

Site Status

Children's Hospital at Montefiore

The Bronx, New York, United States

Site Status

Children's Hospital of Philadelphia, University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

Hospital for Sick Children, Labatt Family Heart Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 19375471 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4886455 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31324444 (View on PubMed)

Related Links

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https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

http://www.nhlbi.nih.gov/

National Heart Lung and Blood Institute (NHLBI) website

https://www.ctotc.org/

Clinical Trials in Organ Transplantation in Children (CTOT-C) website

Other Identifiers

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7U01AI077867-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DAIT CTOTC-04

Identifier Type: -

Identifier Source: org_study_id

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