Organ Transplant Recipients Clinical Trial
Official title:
Complement-activating Anti-human Leucocyte Antigen Donor Specific Antibodies in Solid Organ Transplantation: A Systematic Review and Meta-analysis
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.
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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