Ignite Creation Date:
2024-07-17 @ 10:59 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06472973
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-25
First Post:
2024-06-18
Brief Title:
ADDICTOlogical Intervention in LIVEr Transplantation Recipients
Sponsor:
University Hospital Montpellier
Organization:
University Hospital Montpellier
Study Overview
Official Title:
ADDICTOlogical Intervention in LIVEr Transplantation Recipients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AddictoLIVE
Brief Summary:
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 4day 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
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 4day 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:
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 countriesIn 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 andor 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 boundariesthresholds 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 or secondary indication will result in decreased regular andor 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 11 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 yearsTo 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
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 andor 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 boundariesthresholds 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 or secondary indication will result in decreased regular andor 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 11 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 yearsTo 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None