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Allo-antibodies in Pediatric Heart Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01005316
First received: October 27, 2009
Last updated: June 12, 2014
Last verified: June 2014
  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
Drug: Induction Therapy (anti-T cell antibody induction)
Drug: Tacrolimus (Prograf)
Drug: Mycophenolate Mofetil- MMF (CellCept)
Procedure: Intraoperative plasma exchange/pheresis
Procedure: Short-term post-operative plasmapheresis
Drug: Post-transplant course of intravenous immunoglobulin (IVIG) therapy.
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 Alloantibody 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


Estimated Enrollment: 370
Study Start Date: January 2010
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Non-Sensitized
Cohort A will include participants who are allo-antibody negative (Non-Sensitized) as determined by Luminex LABScreen. Non-sensitized recipients receive steroid-free (no prednisone) maintenance immunosuppression.
Drug: Induction Therapy (anti-T cell antibody induction) Drug: Tacrolimus (Prograf) Drug: Mycophenolate Mofetil- MMF (CellCept)
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
Drug: Induction Therapy (anti-T cell antibody induction) Drug: Tacrolimus (Prograf) Drug: Mycophenolate Mofetil- MMF (CellCept) Procedure: Intraoperative plasma exchange/pheresis Procedure: Short-term post-operative plasmapheresis Drug: Post-transplant course of intravenous immunoglobulin (IVIG) therapy. Drug: Prednisone
Maintenance corticosteroids

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 participants will be allo-antibody negative (less than 10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Group B participants will 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 groups will receive standard transplantation care. This study has no interventions. All participants will undergo regular blood tests, but those in the sensitized group will have additional blood testing done 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 and serious adverse 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 a 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 end-points, 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
Investigators
Study Chair: Stephen A. Webber, MBChB, MRCP Children's Hospital of Pittsburgh
  More 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: June 12, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Allograft
Post Transplant Lymphoproliferative Disorder

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Isoantibodies
Mycophenolate mofetil
Mycophenolic Acid
Prednisone
Rho(D) Immune Globulin
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014