Development of a Predictive Score for the Risk of Infection in the Immediate Post-liver-transplant Period (PREDITH)
Liver transplantation (LT) is the only curative treatment option for patients with severe liver disease. Since 2007, the implementation of the MELD score in liver transplant allocation guidelines has led to a change in the profile of transplant recipients, notably with an increase in the proportion of patients receiving transplants for severe liver failure. Thus, in 2023, nearly 40% of liver transplant recipients whose primary indication for LT was cirrhosis had a MELD score greater than 35 (ABM Scientific Report 2023). These patients with severe pre-transplant liver failure often present with associated organ failure (Acute-on-Chronic Liver Failure, ACLF). Infections are the leading cause of death at 1 year post-transplant for patients transplanted with ACLF and are a major concern for all patients, representing one of the leading causes of death at 3 months post-transplant. Another common complication following LT is acute cellular rejection. Although frequent, this complication is reversible with treatment and results in graft loss in fewer than 5% of cases.
The expression of the HLA-DR marker by monocytes (mHLA-DR) is correlated with immunoparesis and the risk of secondary infection and mortality in patients admitted to critical care. In a prospective, single-center pilot study of 99 liver transplant recipients, the Hepatology and Gastroenterology service at the Croix Rousse Hospital, Hospices Civils de Lyon, demonstrated that the kinetics of mHLA-DR levels measured immediately after transplantation could predict the risk of early significant infection (< 1 month) after transplantation and 1-year post-transplant mortality. The early post-transplant kinetics of mHLA-DR expression recovery appeared to be a more relevant predictor of the risk of early post-transplant infection than a single-point-in-time value. The profile of immune recovery kinetics, as well as a pre-LT MELD score > 30, were associated in multivariate analysis with the risk of developing an infection at 1 month post-LT and with 1-year post-LT survival.
PREDITH study team hypothesize that the implementation of mHLA-DR testing immediately post-LT would enable the development of a predictive score for early post-LT infection combining clinical and biological risk factors for post-LT infection and immune monitoring.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Geschat)
Contacten en locaties
Studiecontact
- Naam: LEBOSSE Fanny, Dr
- Telefoonnummer: +33 4 26 10 93 39
- E-mail: fanny.lebosse@chu-lyon.fr
Studie Contact Back-up
- Naam: DELIGNETTE Marie Charlotte, Dr
- Telefoonnummer: +33 4 26 10 90 70
- E-mail: marie-charlotte.delignette@chu-lyon.fr
Studie Locaties
-
-
-
Clermont-Ferrand, Frankrijk, 63100
- Department of Hepatology and Gastroenterology - CHU de Clermont Ferrand
-
Contact:
- Abergel Armand, Pr
- Telefoonnummer: +33 4 73.75.05.04
- E-mail: aabergel@chu-clermontferrand.fr
-
Lyon, Frankrijk, 69004
- Department of Hepatology and Gastroenterology - Hôpital de la Croix-Rousse
-
Contact:
- LEBOSSE Fanny, Dr
- Telefoonnummer: +33 4 26 10 93 39
- E-mail: fanny.lebosse@chu-lyon.fr
-
Contact:
- DELIGNETTE Marie-Charlotte, Dr
- Telefoonnummer: +33 4 26 10 90 70
- E-mail: marie-charlotte.delignette@chu-lyon.fr
-
Montpellier, Frankrijk, 34090
- Department of Hepatology and Gastroenterology - Hôpital Saint Eloi
-
Contact:
- Bedoya Jose Ursic, Dr
- Telefoonnummer: 33 4 67.33.70.62
- E-mail: jose.ursicbedoya@chu-montpellier.fr
-
Contact:
- Monet Clément, Dr
- Telefoonnummer: +33 4 67.33.02.62
- E-mail: c-monet@chu-montpellier.fr
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Bemonsteringsmethode
Studie Bevolking
Beschrijving
Inclusion Criteria:
Patients awaiting liver transplantation for one of the following indications:
- Compensated cirrhosis complicated by hepatocellular carcinoma
- Chronically decompensated cirrhosis (recurrent gastrointestinal bleeding, refractory ascites, portopulmonary or hepatopulmonary syndrome, hepatic encephalopathy, chronic liver failure)
- Acute decompensated cirrhosis, with or without associated multiple organ failure (ACLF)
- Acute fulminant hepatitis
Final inclusion will be :
- Patients receiving LT AND
- Who provided their consent to participate during the initial enrollment visit AND
- For whom the baseline sample (during the day of the LT) was collected
Exclusion Criteria:
- Minors
- Patients under legal guardianship or conservatorship
- Pregnant or breastfeeding women
- Patients deprived of their liberty
- Patients not enrolled in the social security system
- Refusal to participate in the study
- Patients receiving immunosuppressive therapy prior to LT (with the exception of corticosteroids at a dosage of 40 mg per day for the treatment of alcoholic hepatitis)
- Patient who is a candidate for a combined organ transplant
- Patient receiving other immunomodulatory therapy (such as immune checkpoint inhibitors) prior to LT
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
|---|---|
|
Patients with severe liver disease waiting for liver transplantation (LT)
Only patients with the most frequent Liver transplantation (LT) indications will be eligible: complicated cirrhosis of hepatocellular carcinoma (HCC), acute or chronic decompensation of cirrhosis, with or without multi-visceral and fulminant hepatitis
|
Samples will be collected at the finale inclusion of the day oh the LT, including one sample of Cyto-Chex BCT (4 millilitre mL) .
Same samples will also be collected after LT at days 1,3,5 and 10.
Biological data will be collected at those different times
For the creation of the biobank one samples of Ethylenediaminetetraacetic acid (EDTA) (4 millilitre (mL)), and one PAXgene® sample (2.5mL) will be collected:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Predictive score for the risk of infectious complications
Tijdsspanne: Day 30
|
The primary outcome measure will be the diagnostic performance of a predictive score for early post-Liver Transplant (LT) infectious complications occurring within 30 days after LT.
The predictive score will be derived from mHLA-DR levels measured at predefined time points (Day 0, Day 1, Day 3, Day 5, and Day 10 post-LT), the pre-transplant MELD score, and other clinical or laboratory variables significantly associated with infection risk.
The predic
|
Day 30
|
Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 69HCL25_1061
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .