ADDICTOlogical Intervention in LIVEr Transplantation Recipients

NCT ID: NCT06472973

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

720 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-21

Study Completion Date

2030-11-21

Brief Summary

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Transplantation for end-stage-liver disease (ESLD) in the context of Alcohol-Associated Liver Disease (AALD) has been increasing and represents the main indication for Liver Transplantation (LT) in the world. Alcohol Use Disorder (AUD) is considered a brain chronic disease and requires a transdisciplinary approach that includes medical treatment and behavioral interventions.

In the context of LT, alcohol relapse occurs in 26 % up to 50% of LT recipients. Among Liver transplant recipients for AALD, severe alcoholic relapse (defined as more than 3 alcoholic drinks per day for women and 4/day for men) after LT leads to impaired longterm survival due to recurrent alcoholic cirrhosis (RAC), cardiovascular events and de novo cancer.

Several strategies have been developed to prevent alcohol relapse. After LT, integrating an addiction team into the LT program has been advocated by the latest guidelines in Europe and the United States, in order to bring the management of alcohol-use disorder (AUD) in transplantation units, through the association of psychosocial and pharmacological interventions previously reported in AALD. However, those guidelines were based on descriptive studies, and the effect of this management needs to be confirmed through a randomized, controlled, multicenter study, involving centers that still do not include an addiction team in their LT programs.

This study will therefore assess prospectively and comparatively the impact of an addiction intervention after LT on return to alcohol use rates. We hypothesize that standardized targeted addiction monitoring of Liver Transplant recipients decreases the rates of alcohol relapse two years post-liver transplantation.

Detailed Description

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Liver transplantation (LT) is the only curative option for end-stage liver disease and unresectable hepatocellular carcinoma (HCC) without extrahepatic spread. Alcohol Associated Liver Disease (AALD) has become the most common indication for liver transplantation (LT) in many Western countries.In France, AALD accounts for at least 40% of all LT, between decompensated cirrhosis and HCC, which represents more than 500 patients each year.

One, five and 10-year graft rate and patient survival rate after LT for AALD are at least comparable to those of other indications. Nevertheless, long-term survival rates are hampered by frequent and/or excessive relapse in alcohol consumption. Relapse increases the risk of recurrent alcohol-associated cirrhosis but also of de novo alcohol-induced solid malignancies, mainly cancers of the upper aero digestive tract. Graft and patient survival rates, especially long-term, are thus hindered by the occurrence of excessive relapse.

Relapse rates vary immensely between studies and there is a lack of standardization in the definition of its severity, mainly because it is impossible to define the boundaries/thresholds for "safe consumption". However, there is consensus that harm appears for alcohol intake exceeding three portions per day for males and two for females, for at least 100 days with a sense of loss of control. This pattern of relapse, often described as "severe" can be found between 10 and 26% of patients. Most efforts aiming to reduce post-LT relapse rates focus on improving patient selection. Risk-factors of alcohol relapse often found in literature include short duration of pre-LT sobriety (\<6 months), diagnosis of alcohol dependence, family history of alcohol-use disorder, psychiatric comorbidities including other substance abuse, prior alcohol rehabilitation and female gender. Scores such as HRAR (High Risk Alcoholism Relapse) have also attempted to stratify relapse risk based on pre-LT risk factors. Unfortunately, these criteria are not sensitive enough and most patients who finally benefit from the intervention are in the low to medium risk groups.

It is therefore a priority to utilize also resources in the post-LT setting to decrease alcohol relapse since it is a frequent and relatively difficult to predict event, with a high impact on outcomes after LT. We hypothesize that post-transplant addiction specialist interventions in liver transplant patients with AALD as primary, secondary or tertiary indication will result in decreased regular and/or severe alcohol relapse rate two years post-LT. By extension, this could result in higher graft and patient survival rates, especially in long term.

More recently, our group has performed a retrospective analysis of three centers with different addiction follow-up practices suggesting a benefit on severe relapse rates of addiction specialist intervention after LT for AALD. However, the main limit of this work is the retrospective design with different follow-up periods and duration. We designed a multicenter superiority randomized controlled trial with 2 parallel arms:

* Interventional arm where participants are offered targeted addictology follow-up and participate in addiction consultations
* Control arm where participants have classical follow-up by the transplant specialists of the LT center during the post-transplant follow-up period

The randomization will be elaborated using 1:1 ratio and minimization method. It will be stratified on centers and alcohol consumption history.

According to a French cohort study of patients with liver transplantation for alcohol-related disorders, 25% of them relapsed at 2 years.To account for mortality censoring during follow-up, we will apply a 5% increase of the sample size to reach 720 participants (360 in each arm). The comparison of the primary endpoint between arms will be carried out using intention to treat principle. The time to relapse will be expressed using Kaplan-Meier curves in each arm, and compared using a log-rank test. The effect size will be estimated using Cox proportional.

Conditions

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Alcohol Associated Liver Disease Liver Transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Interventional group

Patients randomized into the interventional arm will participate in an addiction consultation during their hospital stay following LT. The participant's addiction treatment will be based on the number of risk factors identified.

Group Type EXPERIMENTAL

Post-transplant addiction intervention

Intervention Type OTHER

The first addiction consultation will be conducted using the BRENDA method which allows the addiction specialist to carry out a psychosocial assessment, to entrust the results of this assessment to the participant, to answer their questions and to evaluate their reactions. Risk factors for alcohol relapse will be collected: social determinants, male gender, psychiatric comorbidities, duration of alcohol abstinence before LT(≥ or \< 6 months) and young age (\< 40 years). If the addiction specialist notes the presence of at least 3 risk factors for alcohol relapse, targeted addiction follow-up will be proposed to the participant including outpatient consultations with motivational interview at least every 4 weeks +/- pharmacological treatment of alcohol use disorder.In case of alcohol relapse or a period of high vulnerability to relapse, specific hospitalizations can be scheduled. If the participant has \<3 risk factors, an addictology consultation every 6 months at most will be proposed.

Control group

Participants randomized into the control arm will benefit from routine LT follow-up organized by the doctors and/or surgeons of the LT center during the post-transplant follow-up period. Usually, the patients have monthly outpatient visit with their physician during the first year after LT, then bi-monthly during the second year. At present, each center has a very different way of supporting transplant recipients, there is no systematic follow-up by an addictologist. Routine care at each center will be identified before the study set up. The different centers refer patients only after return to alcohol use is perceived in routine consultation or identified through biological alcohol markers. In this case, "the alcohol relapse" event will be noted and patients will be transferred to the addictologic center.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Post-transplant addiction intervention

The first addiction consultation will be conducted using the BRENDA method which allows the addiction specialist to carry out a psychosocial assessment, to entrust the results of this assessment to the participant, to answer their questions and to evaluate their reactions. Risk factors for alcohol relapse will be collected: social determinants, male gender, psychiatric comorbidities, duration of alcohol abstinence before LT(≥ or \< 6 months) and young age (\< 40 years). If the addiction specialist notes the presence of at least 3 risk factors for alcohol relapse, targeted addiction follow-up will be proposed to the participant including outpatient consultations with motivational interview at least every 4 weeks +/- pharmacological treatment of alcohol use disorder.In case of alcohol relapse or a period of high vulnerability to relapse, specific hospitalizations can be scheduled. If the participant has \<3 risk factors, an addictology consultation every 6 months at most will be proposed.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Aged 18 years or above
* Hospitalized for LT for AALD as primary, secondary or tertiary indication
* Discharged from intensive care unit to hepatology or surgery wards

Exclusion Criteria

* Severe alcohol-associated hepatitis as primary indication for liver transplantation
* Impossibility of patient follow up over the next 2 years
* General criteria:

* Refusal or absence of informed consent,
* Non-affiliation to the French national health insurance,
* Persons placed under legal protection, guardianship or curatorship
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hélène DONNADIEU, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Locations

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Besançon University Hospital

Besançon, , France

Site Status RECRUITING

Bordeaux University Hospital

Bordeaux, , France

Site Status RECRUITING

Clermont Ferrand University Hospital

Clermont-Ferrand, , France

Site Status RECRUITING

Dijon University Hospital

Dijon, , France

Site Status RECRUITING

Lille University Hospital

Lille, , France

Site Status RECRUITING

Lyon University Hospital

Lyon, , France

Site Status RECRUITING

Marseille University Hospital

Marseille, , France

Site Status NOT_YET_RECRUITING

Montpellier University Hospital

Montpellier, , France

Site Status RECRUITING

Nice University Hospital

Nice, , France

Site Status RECRUITING

APHP Mondor

Paris, , France

Site Status RECRUITING

APHP Paul Brousse

Paris, , France

Site Status RECRUITING

APHP Salpetrière

Paris, , France

Site Status RECRUITING

Rennes University Hospital

Rennes, , France

Site Status RECRUITING

Strasbourg University Hospital

Strasbourg, , France

Site Status RECRUITING

Toulouse University Hospital

Toulouse, , France

Site Status RECRUITING

Tours University Hospital

Tours, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Hélène DONNADIEU, MD, PhD

Role: CONTACT

0467337020 ext. +33

Other Identifiers

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2023-A02801-44

Identifier Type: REGISTRY

Identifier Source: secondary_id

RECHMPL23_0399

Identifier Type: -

Identifier Source: org_study_id

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