Clinical trial NCT02824354: Nalmefene in Patients With Alcoholic Compensated Cirrhosis for the Treatment of Alcohol Dependence.
Official title: Multicentre, Randomised, Double-blind, Placebo-controlled Trial of Nalmefene in Patients With Alcoholic Compensated Cirrhosis for the Treatment of Alcohol Dependence.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Cirrhosis
Alcohol Dependence
Nalmefene
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2016-07-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Nalmefene is the first drug to obtain Marketing Authorisation in France for reduction of alcohol consumption.

Detailed description: Nalmefene is the first drug to obtain Marketing Authorisation in France for reduction of alcohol consumption. It appears to be significantly more effective in the group of heavy drinkers, while the mean alcohol consumption in studies conducted in cirrhotic patients is greater than 120 g/day.

No data are available concerning nalmefene in alcohol-dependent patients with alcoholic cirrhosis. However, nalmefene could represent an attractive alternative to reduce heavy drinking in patients with alcoholic cirrhosis, with potential improvement of liver function. No comparator is available for nalmefene, as all other molecules require abstinence prior to starting treatment.

Eligibility criteria: Inclusion Criteria:

* the patient has signed and dated the informed consent form,
* blood alcohol concentration \< 0.02% at the screening visit,
* alcohol-dependent patient according to DSM-IV-TR criteria ,
* patient with compensated cirrhosis (cirrhosis demonstrated by clinical and laboratory and/or morphological examinations and/or by a noninvasive test and/or by liver biopsy), Child A or B,
* patient with at least a high drinking risk level (a moderate risk level is defined as a consumption ≥ 60 g of alcohol/day for men and ≥ 40 g of alcohol/day for women),
* male or female, over the age of 18 years, excluding protected majors,
* patient with a stable address and telephone number,
* name and address of a family member who will be contacted in the event of loss of contact with the patient,
* women of childbearing potential:

  * must accept not to become pregnant during the study and,
  * must use an effective method of contraception (adequate contraception is defined as oral, systemic contraception, intrauterine device, diaphragm in combination with spermicide, or condom for the male partner in combination with spermicide) or,
  * must have had their last natural menstruation ≥ 24 months before the screening visit or,
  * must have been surgically sterilized before the screening visit or,
  * must have undergone hysterectomy before the screening visit or,
  * must have no sexual activity with a male partner
* patient covered by French national health insurance.

Exclusion Criteria:

* cirrhosis Child Pugh C (decompensated cirrhosis)
* cirrhosis complicated by hepatocellular carcinoma or type I or II hepatorenal syndrome or poorly controlled portal hypertension,
* severe acute alcoholic hepatitis, not responding to corticosteroids by the 7th day defined by a Lille model \> 0.56 (www.lillemodel.com/score.asp)
* hepatic encephalopathy during the 6 months preceding the screening visit,
* patient with fewer than 6 heavy drinking days during the 4 weeks preceding the screening visit (a heavy drinking day is defined as alcohol consumption of ≥ 60 g/day for men, and ≥ 40 g/day for women),
* patient with at least 14 consecutive days of abstinence during the 4 weeks preceding the screening visit,
* patient with a CIWA-Ar score (Revised Clinical Institute Withdrawal Assessment for Alcohol) ≥ 10,
* patient with:
* a disorder other than alcohol or nicotine dependence, as evaluated on the MINI (Mini-International Neuropsychiatric Interview)
* antisocial personality disorder evaluated with the MINI questionnaire,
* other disorders for which treatment must take priority to the treatment of alcohol dependence, or which are likely to interfere with the study treatment or compromise adherence to treatment,
* cannabis use does not constitute an exclusion criterion except when it meets the criterion of cannabis dependence
* patient with a suicide risk evaluated using the suicidal tendency module of the MINI (the patient answers "Yes" to one of questions C2, C3, C4, C5 or C6 of the questionnaire),
* patient with a history of delirium tremens or alcohol withdrawal seizures,
* ongoing use of addictive substances other than cannabis, nicotine or benzodiazepines,
* presence of a disorder of comprehension, mental retardation or encephalopathy,
* presence of clinically significant unstable disease (e.g.: renal failure, cardiovascular, pulmonary, gastrointestinal, gastrointestinal, endocrine, neurological, infectious, neoplastic disease or metabolic disorders,
* clinically significant ECG abnormalities,
* history of serious drug allergy or hypersensitivity to nalmefene,
* ongoing or recent treatment (during the 3 months preceding the screening visit) with disulfiram, acamprosate, topiramate, naltrexone, carbimide, or opioid antagonists,
* ongoing or recent treatment (1 week preceding the screening visit) with opioid agonists or partial agonists,
* ongoing or recent treatment (8 weeks preceding the screening visit) with antipsychotics or antidepressants,
* patient taking or who has taken concomitant medications (see supplementary table),
* patient with another disease or taking medications, which, in the investigator's opinion, could interfere with evaluations of safety, tolerability and efficacy,
* treatment with an investigational medicinal product during the 30 days preceding the screening visit,
* ongoing or recent participation (during the 4 weeks preceding the screening visit) in a drinking disorders treatment or support programme, including Alcoholics Anonymous, disintoxication treatment and treatment of alcohol withdrawal symptoms,
* pregnancy or breastfeeding,
* patient who, in the investigator's opinion, has little chance of complying with the protocol or unsuitable for the study for any other reason,
* patient who has already participated in a clinical trial on nalmefene.

Primary outcomes:
measure: Reduction of the number of monthly heavy drinking days after 6 months of treatment compared to baseline.
timeFrame: 6 months
Secondary outcomes:
measure: The number of non-drinking days during the treatment period; nalmefene arm versus placebo arm,
timeFrame: 6 months
measure: Evaluation of craving; nalmefene arm responders versus nalmefene arm non-responders
timeFrame: 6 months
measure: Course of liver function after 6 months of treatment compared to baseline
timeFrame: 6 months
measure: 6 months survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
Study officials:
affiliation: CHU Amiens
name: Eric NGUYEN-KHAC, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: