Allo-Antibodies in Pediatric Heart Transplantation

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01005316
First received: October 27, 2009
Last updated: October 5, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention
Pediatric Heart Transplantation
Pediatric Heart Transplant Recipients
Drug: Induction Therapy
Drug: Tacrolimus
Drug: Mycophenolate Mofetil
Procedure: Intraoperative plasma exchange/pheresis
Procedure: Short-term post-operative plasmapheresis
Drug: Immunoglobulins, Intravenous
Drug: Prednisone

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Allo-Antibodies in Pediatric Heart Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Composite of the Incidence of Death, Retransplantation or Rejection with Hemodynamic Compromise [ Time Frame: At month 12 post-transplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of Allo-Antibody Production Post-Transplantation [ Time Frame: Study enrollment to end of study ] [ Designated as safety issue: Yes ]
    Incidence of de novo alloantibody production post-transplantation impact on graft and participant outcomes in cohort A participants.

  • Time to Production of Post-Transplant de novo Allo-Antibodies [ Time Frame: Study enrollment to end of study ] [ Designated as safety issue: Yes ]
    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).

  • Incidence of Death While on Transplant Wait-List [ Time Frame: Study enrollment to time of transplant ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Pre-transplant

  • Time from Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing [ Time Frame: Study enrollment to time of transplant ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Pre-transplant

  • Presence and Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing [ Time Frame: Study enrollment to time of transplant ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Pre-transplant

  • Presence of Anti-MICA Antibodies by Luminex TM assay [ Time Frame: Study enrollment to time of transplant ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Pre-transplant

  • Overall Participant and Graft Survival [ Time Frame: Time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Presence of C4d on Endomyocardial Biopsy (EMB) [ Time Frame: time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Incidence of Rehospitalizations [ Time Frame: Time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Incidence of Severe Infections [ Time Frame: time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Time to Diagnosis of Chronic Rejection (Graft Coronary Artery Disease) [ Time Frame: Time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Time to Post-Transplantation Lymphoproliferative Disorder [ Time Frame: Time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Time to New-Onset Diabetes Mellitus [ Time Frame: Time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant

  • Frequency and Time to Acute Rejection [ Time Frame: Time of transplant to end of study ] [ Designated as safety issue: Yes ]
    Cohort A and Cohort B: Post-transplant


Biospecimen Retention:   Samples With DNA
Blood collection and biopsy tissue samples

Enrollment: 370
Study Start Date: January 2010
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cohort A: Non-Sensitized

Cohort A will include participants who are allo-antibody 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®).
Drug: Induction Therapy
Per standard of care guidelines for immunosuppression at each clinical site.
Other Name: anti-T cell antibody induction
Drug: Tacrolimus
Per standard of care guidelines for immunosuppression at each clinical site.
Other Name: Prograf®
Drug: Mycophenolate Mofetil
Per standard of care guidelines for immunosuppression at each clinical site.
Other Names:
  • CellCept®
  • MMF
Cohort B: Sensitized

Cohort B will include participants who are allo-antibody 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®).
Drug: Induction Therapy
Per standard of care guidelines for immunosuppression at each clinical site.
Other Name: anti-T cell antibody induction
Drug: Tacrolimus
Per standard of care guidelines for immunosuppression at each clinical site.
Other Name: Prograf®
Drug: Mycophenolate Mofetil
Per standard of care guidelines for immunosuppression at each clinical site.
Other Names:
  • CellCept®
  • MMF
Procedure: Intraoperative plasma exchange/pheresis
Per standard of care guidelines for immunosuppression at each clinical site.
Other Name: plasmapheresis
Procedure: Short-term post-operative plasmapheresis
Per standard of care guidelines for immunosuppression at each clinical site.
Other Name: pheresis
Drug: Immunoglobulins, Intravenous
Post-transplant course of intravenous immunoglobulin therapy per standard of care guidelines for immunosuppression at each clinical site.
Other Name: IVIG
Drug: Prednisone
Maintenance corticosteroids per standard of care guidelines for immunosuppression at each clinical site.
Other Name: corticosteroid

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pediatric heart transplantation candidates
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01005316

Locations
United States, Massachusetts
Children's Hospital Boston, Harvard Medical School
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis Children's Hospital, Washington University
St. Louis, Missouri, United States, 63110
United States, New York
Children's Hospital at Montefiore
Bronx, New York, United States, 10467
Children's Hospital of New York, Columbia University Medical Center
New York, New York, United States, 10032
United States, Pennsylvania
Children's Hospital of Philadelphia, University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Canada, Ontario
Hospital for Sick Children, Labatt Family Heart Centre
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Study Chair: Stephen A. Webber, MBChB, MRCP Children's Hospital of Pittsburgh
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01005316     History of Changes
Other Study ID Numbers: DAIT CTOTC-04  U01A1077867 01 
Study First Received: October 27, 2009
Last Updated: October 5, 2015
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
cohort study
allo-antibodies
allosensitization

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Isoantibodies
Mycophenolate mofetil
Mycophenolic Acid
Rho(D) Immune Globulin
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on February 07, 2016