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

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03438058
• Other study ID #: ALPINIST001
• Status: Completed
• Phase: N/A
• First received: February 1, 2018
• Last updated: February 15, 2018
• Start date: January 2017
• Est. completion date: February 2018

Study information

• Verified date: February 2018
• Source: Paris Translational Research Center for Organ Transplantation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7547
• Est. completion date: February 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Organ Transplant Recipients

Intervention

Other:
• Graft survival and/or Rejection appearance

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Paris Translational Research Center for Organ Transplantation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Allograft Survival rate	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)	death censored allograft survival at minimum 1 year of follow up
Secondary	Allograft Rejection rate	To evaluate the impact of complement-activating anti-HLA DSA on the risk of antibody mediated rejection or biopsy proven histological allograft injury	rejection rate during follow up (at minimum 3 months post transplantation) or rejection defined by biopsy at inclusion