Alloantibodies in Pediatric Heart Transplantation

NCT01005316 | Terminated Results DMC

• 2 other identifiers: DAIT CTOTC-047U01AI077867-02
• Study Type: observational
• Target: 290
• Locations: 2 countries
• Sites: 8

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.

Conditions

Pediatric Heart Transplantation; Pediatric Heart Transplant Recipients

Keywords

cohort study; allo-antibodies; allosensitization

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation

  This is a composite outcome of death, graft loss or rejection with hemodynamic compromise. Rejection was considered to be with hemodynamic compromise if the rejection event had new onset echocardiographically measured from fractional shortening \<26% with ≥5% fall from last echocardiogram or the rejection event had new onset of heart failure.

  12 months post-transplantation

Secondary Outcomes (16)

• Time to Production of Post-Transplant de Novo Donor-specific Alloantibodies

  Transplantation to first year post transplant (up to 12 months post transplant).

• Percentage of Participants Positive for de Novo Donor-Specific Alloantibody Production in the First Year Post-Transplantation

  Transplantation to first year post transplant (up to 12 months post transplant).

• Percentage of Participants- Mortality While on Transplantation Wait-List

  Pre-transplantation

• Time From Participant Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing

  Study enrollment to transplantation

• Percentage of Participants With the Presence of Anti-HLA IgG Antibodies by Luminex SA Testing

  Pre-transplantation

Study Arms (2)

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®).

Drug: Induction Therapy; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

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®).

Drug: Induction Therapy; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Intraoperative plasma exchange/pheresis; Procedure: Short-term post-operative plasmapheresis; Drug: Immunoglobulins, Intravenous; Drug: Prednisone

Interventions

Induction Therapy DRUG

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

Also known as: anti-T cell antibody induction

Cohort A: Non-Sensitized; Cohort B: Sensitized

Tacrolimus DRUG

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

Also known as: Prograf®

Cohort A: Non-Sensitized; Cohort B: Sensitized

Mycophenolate Mofetil DRUG

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

Also known as: CellCept®, MMF

Cohort A: Non-Sensitized; Cohort B: Sensitized

Intraoperative plasma exchange/pheresis PROCEDURE

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

Also known as: plasmapheresis

Cohort B: Sensitized

Short-term post-operative plasmapheresis PROCEDURE

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

Also known as: pheresis

Cohort B: Sensitized

Immunoglobulins, Intravenous DRUG

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

Also known as: IVIG

Cohort B: Sensitized

Prednisone DRUG

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

Also known as: corticosteroid

Cohort B: Sensitized

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric heart transplantation candidates

You may qualify if:

• All participants listed for heart transplantation at participating CTOT-C study sites.

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (8)

Children's Hospital Boston, Harvard Medical School

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital, Washington University

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10032, United States

Location

Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Children's Hospital of Philadelphia, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Hospital for Sick Children, Labatt Family Heart Centre

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (3)

• 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.

  PMID: 19375471 BACKGROUND

• 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.

  PMID: 4886455 BACKGROUND

• 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.

  PMID: 31324444 DERIVED

Related Links

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

Biospecimen

Retention: SAMPLES WITH DNA

Blood collection and biopsy tissue samples

MeSH Terms

Interventions

Neoadjuvant Therapy; Tacrolimus; Mycophenolic Acid; Blood Component Removal; Plasmapheresis; Immunoglobulins, Intravenous; Prednisone; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Study enrollment closed December 2013:target enrollment was not met (78% of target).Not all participants recv'd the planned 3 year follow-up. Participants were followed for a year after enrollment closure then enrolled into CTOTC-09 (NCT02752789).

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Stephen A. Webber, MBChB, MRCP

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2009
• First Posted: October 30, 2009
• Study Start: January 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 20, 2017
• Results First Posted: April 20, 2017

Record last verified: 2017-03

Locations

US (7); CA (1)