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Complement-activating Anti-human Leucocyte Antigen Donor Specific Antibodies in Solid Organ Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03438058
Recruitment Status : Completed
First Posted : February 19, 2018
Last Update Posted : February 19, 2018
Sponsor:
Information provided by (Responsible Party):
Professor Alexandre Loupy, Paris Translational Research Center for Organ Transplantation

Brief Summary:

This project will involve a systematic literature review and meta-analysis of studies assessing the impact of complement-activating anti-Human Leukocyte Antigen (HLA) donor specific antibodies (DSA) on the allograft survival rate and on the rejection rate.

This meta-analysis will assess the role of complement activating anti-HLA DSAs across the entire transplant field including kidney, liver, lung and heart transplant recipient's studies.


Condition or disease Intervention/treatment
Organ Transplant Recipients Other: Graft survival and/or Rejection appearance

Detailed Description:

BACKGROUND:

Organ transplantation has emerged as the treatment of choice for patients with end-stage chronic disease, which is an increasing burden in industrialized and newly-industrializing societies. For example, the global burden of end-stage renal disease in 2017 is estimated to be 3,900,000 with an ~6% growth rate, which is significantly greater than world population growth. Today, over one million people worldwide live with organ transplants, and another 120,000 organs transplanted each year.

Despite progress in transplantation, allograft rejection remains a major threat to allograft health, with thousands of allografts failing every year worldwide due to organ rejection. Failed allografts create immediate and severe consequences for patients in terms of mortality and morbidity, while generating billions in extra costs to health care systems.

One of the most important advances in transplant medicine was the recognition that anti-human lymphocyte antigen (anti-HLA) antibodies are destructive. Recently, lots of studies recognized the capacity of anti-HLA antibodies to activate complement and determined that complement activation magnifies the cytotoxic potential of these antibodies. Over the last decade, studies have reported that complement-activation is highly associated with allograft rejection and failure, with varying magnitudes of effect. In addition, more recent studies have suggested that beyond kidney allografts, these antibodies could have a broad universal deleterious effect in other solid organ transplants such a heart, liver and lung allografts.

MAIN OUTCOMES AND MEASURES:

Evaluate the clinical relevance of complement-activating anti-HLA antibodies at a population level, by performing a meta-analysis across solid organ transplants (kidney, liver, heart and lung transplant patients) to determine the magnitude of the association between the presence of complement-activating antibody and the related risk for allograft failure and risk of rejection.

DESIGN:

This meta-analysis will report in adherence with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the reporting Meta-Analyses of Observational Studies in Epidemiology (MOOSE).

A comprehensive search will be design and conduct by an experienced librarian with input from the study investigators. Controlled vocabulary supplemented with keywords will be used to search for complement-activating anti-human leucocyte antigen donor-specific antibodies in human solid organ transplantation in any language. The following databases will be included: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.

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Study Type : Observational
Actual Enrollment : 7547 participants
Observational Model: Other
Time Perspective: Retrospective
Official Title: Complement-activating Anti-human Leucocyte Antigen Donor Specific Antibodies in Solid Organ Transplantation: A Systematic Review and Meta-analysis
Actual Study Start Date : January 2017
Actual Primary Completion Date : January 2018
Actual Study Completion Date : February 2018

Group/Cohort Intervention/treatment
With complement-activating anti-HLA DSAs
Patients with complement-activating anti-HLA DSAs either C1q, C3d, C4d and IgG subclass
Other: Graft survival and/or Rejection appearance
Without complement-activating anti-HLA DSAs
Patients with anti-HLA DSAs but without the ability to activate the complement (either C1q, C3d, C4d and IgG subclass)
Other: Graft survival and/or Rejection appearance
Without DSAs and without complement-activating DSAs
Matching group of patients without DSAs and without complement-activating DSAs
Other: Graft survival and/or Rejection appearance



Primary Outcome Measures :
  1. Allograft Survival rate [ Time Frame: death censored allograft survival at minimum 1 year of follow up ]
    To assess the impact of complement-activating anti-Human Leukocyte Antigen (HLA) donor specific antibodies (DSA) on the allograft survival rate in solid organ transplant patients (Heart, Kidney, Lung, Liver and Small Bowel transplant recipients)


Secondary Outcome Measures :
  1. Allograft Rejection rate [ Time Frame: rejection rate during follow up (at minimum 3 months post transplantation) or rejection defined by biopsy at inclusion ]
    To evaluate the impact of complement-activating anti-HLA DSA on the risk of antibody mediated rejection or biopsy proven histological allograft injury



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The eligible studies include all solid organ transplant patients (kidney, liver, lung, heart, and intestinal transplantation), both adult or paediatric patients in which complement-activating anti-HLA DSAs have been measured (either C1q, C3d, and C4d or their IgG3 subclass). In those studies data on allograft survival and rejection rate have to be measure.
Criteria

Inclusion Criteria:

  • Study design:

Studies of any relevant design and in any language on the impact of complement-activating anti-HLA DSAs on long-term graft survival and/or the risk of rejection will be initially selected.

  • eligible studies: The eligible studies include all solid organ transplant patients (kidney, liver, lung, heart, and intestinal transplantation), both adult or paediatric patients.
  • Measurement:

Anti-HLA DSAs detect by the single antigen Luminex bead technique (SAB) will be required for the DSA detection technique. Complement-activating anti-HLA DSAs will be defined according to their ability to bind C1q, C3d, and C4d or their IgG3 subclass.

Exclusion Criteria:

  • Animal studies
  • Ex vivo studies
  • Methodological studies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03438058


Sponsors and Collaborators
Paris Translational Research Center for Organ Transplantation
Investigators
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Principal Investigator: Carmen Lefaucheur, PhD Paris Translational Research Center for Organ Transplantation
Principal Investigator: Alexandre Loupy, PhD Paris Translational Research Center for Organ Transplantation

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Professor Alexandre Loupy, Paris Translational Research Center for Organ Transplantation
ClinicalTrials.gov Identifier: NCT03438058    
Other Study ID Numbers: ALPINIST001
First Posted: February 19, 2018    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No access to the individual participant data

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Professor Alexandre Loupy, Paris Translational Research Center for Organ Transplantation:
Solid Organ Transplantation
Graft survival
Rejection
Complement-activating anti-HLA DSA
Meta-analysis
Prognosis
Additional relevant MeSH terms:
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Antibodies
Complement System Proteins
Immunologic Factors
Physiological Effects of Drugs