Organ Transplant RecipientsNCT03438058
Complement-activating Anti-human Leucocyte Antigen Donor Specific Antibodies in Solid Organ Transplantation
An observational study of Organ Transplant Recipients, run by Paris Translational Research Center for Organ Transplantation.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Organ Transplant Recipients
- What is being tested?
- Graft survival and/or Rejection appearance
- How many people
- 7,547 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Feb 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Animal studies
- Ex vivo studies
- Methodological studies
About this study
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.
Read the 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.
- Conditions
- Organ Transplant Recipients
- Being tested
- Graft survival and/or Rejection appearance
- Keywords
- Solid Organ Transplantation, Graft survival, Rejection, Complement-activating anti-HLA DSA, Meta-analysis, Prognosis
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Graft survival and/or Rejection appearanceOther
| Study group | Role | What they receive |
|---|---|---|
| With complement-activating anti-HLA DSAs | Patients with complement-activating anti-HLA DSAs either C1q, C3d, C4d and IgG subclass Receives: 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) Receives: 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 Receives: Other: Graft survival and/or Rejection appearance |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: death censored allograft survival at minimum 1 year of follow up
Secondary outcomes (1)
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
Measured: rejection rate during follow up (at minimum 3 months post transplantation) or rejection defined by biopsy at inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study startJan 2017
- Primary completionJan 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Organ Transplant RecipientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 7,547 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paris Translational Research Center for Organ Transplantation
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Alexandre Loupy, Paris Translational Research Center for Organ Transplantation
- Investigators
- Carmen Lefaucheur, PhD, Principal investigator, Paris Translational Research Center for Organ TransplantationAlexandre Loupy, PhD, Principal investigator, Paris Translational Research Center for Organ Transplantation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03438058
- Sponsor's protocol ID
- ALPINIST001
- Status last verified
- Feb 2018
- First submitted
- 1 Feb 2018
- Last updated
- 19 Feb 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No access to the individual participant data
Publications
Bouquegneau A, Loheac C, Aubert O, Bouatou Y, Viglietti D, Empana JP, Ulloa C, Murad MH, Legendre C, Glotz D, Jackson AM, Zeevi A, Schaub S, Taupin JL, Reed EF, Friedewald JJ, Tyan DB, Susal C, Shapiro R, Woodle ES, Hidalgo LG, O'Leary J, Montgomery RA, Kobashigawa J, Jouven X, Jabre P, Lefaucheur C, Loupy A. Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis. PLoS Med. 2018 May 25;15(5):e1002572. doi: 10.1371/journal.pmed.1002572. eCollection 2018 May.
PubMed 29799874
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Complement-activating Anti-human Leucocyte Antigen Donor Specific Antibodies in Solid Organ Transplantation: A Systematic Review and Meta-analysis
- ClinicalTrials.gov ID
- NCT03438058
- Acronym / sponsor ID
- ALPINIST001
- Conditions
- Organ Transplant Recipients
- Keywords
- Solid Organ Transplantation, Graft survival, Rejection, Complement-activating anti-HLA DSA, Meta-analysis, Prognosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7,547 participants (actual)
- Lead sponsor
- Paris Translational Research Center for Organ TransplantationUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| With complement-activating anti-HLA DSAs | – | Other: Graft survival and/or Rejection appearancePatients with complement-activating anti-HLA DSAs either C1q, C3d, C4d and IgG subclass |
| Without complement-activating anti-HLA DSAs | – | Other: Graft survival and/or Rejection appearancePatients with anti-HLA DSAs but without the ability to activate the complement (either C1q, C3d, C4d and IgG subclass) |
| Without DSAs and without complement-activating DSAs | – | Other: Graft survival and/or Rejection appearanceMatching group of patients without DSAs and without complement-activating DSAs |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- Animal studies
- Ex vivo studies
- Methodological studies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Graft survival and/or Rejection appearance | Other | With complement-activating anti-HLA DSAs, Without DSAs and without complement-activating DSAs, Without complement-activating anti-HLA DSAs |
Primary outcome
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)
1 secondary outcome
Allograft Rejection rate
Time frame: rejection rate during follow up (at minimum 3 months post transplantation) or rejection defined by biopsy at inclusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2018.
- Derived from this study: PubMed 29799874Bouquegneau A, Loheac C, Aubert O, Bouatou Y, Viglietti D, Empana JP, Ulloa C, Murad MH, Legendre C, Glotz D, Jackson AM, Zeevi A, Schaub S, Taupin JL, Reed EF, Friedewald JJ, Tyan DB, Susal C, Shapiro R, Woodle ES, Hidalgo LG, O'Leary J, Montgomery RA, Kobashigawa J, Jouven X, Jabre P, Lefaucheur C, Loupy A. Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis. PLoS Med. 2018 May 25;15(5):e1002572. doi: 10.1371/journal.pmed.1002572. eCollection 2018 May.
- Individual participant dataSharing planned: No. No access to the individual participant data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carmen Lefaucheur, PhD principal investigator
Paris Translational Research Center for Organ Transplantation
Alexandre Loupy, PhD principal investigator
Paris Translational Research Center for Organ Transplantation
Questions about this trial
What is this clinical trial studying?
An observational study of Organ Transplant Recipients, run by Paris Translational Research Center for Organ Transplantation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Allograft Survival rate (time frame: death censored allograft survival at minimum 1 year of follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03438058, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2018.