Clinical trial • Gastroenterology
ACETYLCYSTEINE for Alcoholic hepatitis
Clinical trial of ACETYLCYSTEINE for Alcoholic hepatitis.
Overview
- Trial Therapeutic Area
- Gastroenterology
- Trial Disease
- Alcoholic hepatitis
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 22-07-2025
- First CTIS Authorization Date
- 17-10-2025
Trial design
Randomised, three-arm randomized double-blind design. arm 1: from day 1 to day 5: prednisolone 40 mg/day (oral) + n-acetylcysteine (intravenous); from day 6 to day 30: prednisolone 40 mg/day (oral); from day 31 to day 60: placebo (oral). arm 2: from day 1 to day 5: prednisolone 40 mg/day (oral) + placebo (intravenous); from day 6 to day 30: prednisolone 40 mg/day (oral); from day 31 to day 60: placebo (oral). arm 3: from day 1 to day 5: prednisolone 40 mg/day (oral) + placebo (intravenous); from day 6 to day 30: prednisolone 40 mg/day (oral); from day 31 to day 60: prednisolone (oral) with tapering doses: 40 mg/day (day 31-38), 30 mg/day (day 38-45), 20 mg/day (day 45-52), 10 mg/day (day 52-60).-controlled trial in France.
- Randomised
- Yes
- Comparator
- Three-arm randomized double-blind design. Arm 1: From day 1 to day 5: Prednisolone 40 mg/day (oral) + N-acetylcysteine (intravenous); From day 6 to day 30: Prednisolone 40 mg/day (oral); From day 31 to day 60: Placebo (oral). Arm 2: From day 1 to day 5: Prednisolone 40 mg/day (oral) + placebo (intravenous); From day 6 to day 30: Prednisolone 40 mg/day (oral); From day 31 to day 60: Placebo (oral). Arm 3: From day 1 to day 5: Prednisolone 40 mg/day (oral) + placebo (intravenous); From day 6 to day 30: Prednisolone 40 mg/day (oral); From day 31 to day 60: Prednisolone (oral) with tapering doses: 40 mg/day (day 31-38), 30 mg/day (day 38-45), 20 mg/day (day 45-52), 10 mg/day (day 52-60).
- Target Sample Size
- 477
- Trial Duration For Participant
- 360
Stratification factors
- center
Eligibility
Recruits 477 No vulnerable population selected (isVulnerablePopulationSelected: false). Informed consent is required from patients ("Patients having provided written informed consent to participate"). Subject information and informed consent forms are provided (documents: "L1_SIS ans ICF patients_Redacted" and a separate "L1_SIS ans ICF trusted person_Redacted"), indicating provision for a trusted person document if relevant..
- Vulnerable Population
- No vulnerable population selected (isVulnerablePopulationSelected: false). Informed consent is required from patients ("Patients having provided written informed consent to participate"). Subject information and informed consent forms are provided (documents: "L1_SIS ans ICF patients_Redacted" and a separate "L1_SIS ans ICF trusted person_Redacted"), indicating provision for a trusted person document if relevant.
Inclusion criteria
- {"criterion_text":"- Patients aged 18-75"}
- {"criterion_text":"- Alcohol consumption of more than 40g/day (women) and 50g/day (men)"}
- {"criterion_text":"- Recent onset of jaundice (<3 months)"}
- {"criterion_text":"- Biopsy proven alcoholic hepatitis (transjugular liver biopsy)"}
- {"criterion_text":"- Maddrey’s discriminant function ≥ 32, defining severe alcoholic hepatitis"}
- {"criterion_text":"- MELD score ≥ 17"}
- {"criterion_text":"- Patients covered with social insurance"}
- {"criterion_text":"- Patients having provided written informed consent to participate"}
Exclusion criteria
- {"criterion_text":"- Hepatocellular carcinoma"}
- {"criterion_text":"- Untreated bacterial infection. Patients on antibiotics to treat ongoing infection can be included if the investigator feels the sepsis is under control."}
- {"criterion_text":"- Tuberculosis < 5 years"}
- {"criterion_text":"- Positive blood PCR in patients with positive antibodies against HCV"}
- {"criterion_text":"- Patient carrying HBV or HIV"}
- {"criterion_text":"- Treatment with corticosteroids, immunosuppression therapy or budesonide within 6 months before the study"}
- {"criterion_text":"- Uncontrolled gastrointestinal bleeding"}
- {"criterion_text":"- Previous severe allergy or hypersensitivity to N-acetylcysteine (anaphylactic shock, Quincke edema, severe urticaria)"}
- {"criterion_text":"- Hypersensitivity to any component of the medication"}
- {"criterion_text":"- MELD score <17"}
- {"criterion_text":"- Type 1 hepatorenal syndrome before the initiation of treatment"}
- {"criterion_text":"- Severe extrahepatic disease, with life expectancy < 6 months"}
- {"criterion_text":"- Any malignant tumor < 2 years (except skin carcinomas)"}
- {"criterion_text":"- Ongoing viral or parasitic infection"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Rate of patients alive with compensated liver disease defined as a MELD score <17 at 90 days. MELD score will be calculated according to the formula given in Dunn et al. Hepatology 2005: MELD = 9.57 x ln (creatinine in mg/dL) + 3.78 x ln (bilirubin in mg/dL) + 11.2 x ln (INR) + 6.43","definition_or_measurement_approach":"MELD score calculation as specified: MELD = 9.57 x ln (creatinine in mg/dL) + 3.78 x ln (bilirubin in mg/dL) + 11.2 x ln (INR) + 6.43; endpoint assessed at 90 days as rate of patients with MELD <17 (compensated liver disease)."}
Secondary endpoints
- {"endpoint_text":"-\tOverall survival at 90 and 360 days ; -\tRate of patients alive with compensated liver disease defined by a MELD score <17 at 30-days, 60-days,180 and 360 days","definition_or_measurement_approach":"Overall survival measured at 90 and 360 days. Rate of patients with MELD <17 measured at 30, 60, 180 and 360 days using the MELD formula."}
- {"endpoint_text":"Therapeutic response at day 7 assessed by the rate of patients with a Lille score <0.45 as well as the Lille score treated as a continuous variable (assessing the degree of therapeutic response)","definition_or_measurement_approach":"Therapeutic response assessed at day 7 using Lille score; responder defined as Lille score <0.45; Lille score also analyzed as continuous variable."}
- {"endpoint_text":"-\tCumulative incidence of infection within the first 90 days; -\tCumulative incidence of hepatorenal syndrome within the first 90 days; -\tSerious adverse events within the first 90 days","definition_or_measurement_approach":"Cumulative incidence of specified events (infections, hepatorenal syndrome) and recording of serious adverse events within first 90 days."}
Recruitment
- Planned Sample Size
- 477
- Recruitment Window Months
- 59
- Consent Approach
- Written informed consent is required from participants ("Patients having provided written informed consent to participate"). Subject information and consent forms are provided (documents include "L1_SIS ans ICF patients_Redacted"). A separate 'trusted person' informed consent document is available ("L1_SIS ans ICF trusted person_Redacted"). Consent materials include French translations (protocol and titles include French translations). No assent or paediatric consent procedures are indicated.
Geography
- Total Number Of Sites
- 21
- Total Number Of Participants
- 477
France
- Earliest CTIS Part Ii Submission Date
- 06-10-2025
- Latest Decision Or Authorization Date
- 17-10-2025
- Processing Time Days
- 11
- Number Of Sites
- 21
- Number Of Participants
- 477
Sites
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Service de Gastro-entérologie adultes – Maladies de l’appareil digestif
- Principal Investigator Name
- Alexandre Louvet
- Principal Investigator Email
- alexandre.louvet@chu-lille.fr
- Contact Person Name
- Alexandre Louvet
- Contact Person Email
- alexandre.louvet@chu-lille.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Service Hépatologie et Addictologie
- Principal Investigator Name
- François Bailly
- Principal Investigator Email
- francois.baillye@chu-lyon.fr
- Contact Person Name
- François Bailly
- Contact Person Email
- francois.baillye@chu-lyon.fr
- Site Name
- Centre Hospitalier Universitaire De Dijon
- Department Name
- Service d’Hépato-gastro-entérologie
- Principal Investigator Name
- Marianne Latournerie
- Principal Investigator Email
- marianne.latournerie@chu-dijon.fr
- Contact Person Name
- Marianne Latournerie
- Contact Person Email
- marianne.latournerie@chu-dijon.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Service des Maladies de l'appareil digestif
- Principal Investigator Name
- Florent Artru
- Principal Investigator Email
- florent.artru@univ-rennes.fr
- Contact Person Name
- Florent Artru
- Contact Person Email
- florent.artru@univ-rennes.fr
- Site Name
- Centre Hospitalier Universitaire De Nice
- Department Name
- Pôle de Référence Hépatogastroentérologie et Oncologie Digestive
- Principal Investigator Name
- Rodolphe Anty
- Principal Investigator Email
- anty.r@chu-nice.fr
- Contact Person Name
- Rodolphe Anty
- Contact Person Email
- anty.r@chu-nice.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Service d’Hépato-gastro-entérologie et Transplantation
- Principal Investigator Name
- José Ursic-Bedoya
- Principal Investigator Email
- jose.ursicbedoya@chu-montpellier.fr
- Contact Person Name
- José Ursic-Bedoya
- Contact Person Email
- jose.ursicbedoya@chu-montpellier.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Service d’Hépatologie
- Principal Investigator Name
- Chrisophe Bureau
- Principal Investigator Email
- bureau.c@chu-toulouse.fr
- Contact Person Name
- Chrisophe Bureau
- Contact Person Email
- bureau.c@chu-toulouse.fr
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- Service d’Hépato-gastro-entérologie
- Principal Investigator Name
- Agnès Bonadona
- Principal Investigator Email
- abonadona@chu-grenoble.fr
- Contact Person Name
- Agnès Bonadona
- Contact Person Email
- abonadona@chu-grenoble.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service d'Hépatologie
- Principal Investigator Name
- Nicolas Carbonell
- Principal Investigator Email
- nicolas.carbonell@aphp.fr
- Contact Person Name
- Nicolas Carbonell
- Contact Person Email
- nicolas.carbonell@aphp.fr
- Site Name
- L’Hopital Alexandra Lepeve
- Department Name
- Service d’Hépato Gastro-entérologie
- Principal Investigator Name
- Juliette Verlynde
- Principal Investigator Email
- Juliette.verlynde@ch-dunkerque.fr
- Contact Person Name
- Juliette Verlynde
- Contact Person Email
- Juliette.verlynde@ch-dunkerque.fr
- Site Name
- Centre Hospitalier De Valenciennes
- Department Name
- Service des Maladies de l'Appareil Digestif et de la Nutrition
- Principal Investigator Name
- Faustine Wartel
- Principal Investigator Email
- wartel-f@ch-valenciennes.fr
- Contact Person Name
- Faustine Wartel
- Contact Person Email
- wartel-f@ch-valenciennes.fr
- Site Name
- Centre Hospitalier Universitaire De Caen Normandie
- Department Name
- Service d’Hépato Gastro-entérologie
- Principal Investigator Name
- Isabelle Ollivier
- Principal Investigator Email
- ollivierhourmand-i@chu-caen.fr
- Contact Person Name
- Isabelle Ollivier
- Contact Person Email
- ollivierhourmand-i@chu-caen.fr
- Site Name
- Centre Hospitalier Universitaire D'Angers
- Department Name
- Service d’Hépato-gastro-entérologie
- Principal Investigator Name
- Adrien Lannes
- Principal Investigator Email
- adrien.lannes@chu-angers.fr
- Contact Person Name
- Adrien Lannes
- Contact Person Email
- adrien.lannes@chu-angers.fr
- Site Name
- CHU Besancon
- Department Name
- Service d’Hépatologie
- Principal Investigator Name
- Thierry Thévenot
- Principal Investigator Email
- tthevenot@chu-besancon.fr
- Contact Person Name
- Thierry Thévenot
- Contact Person Email
- tthevenot@chu-besancon.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Service d’hépato-gastro-entérologie et assistance nutritive
- Principal Investigator Name
- Valentin Rolle
- Principal Investigator Email
- valentin.rolle@chu-poitiers.fr
- Contact Person Name
- Valentin Rolle
- Contact Person Email
- valentin.rolle@chu-poitiers.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Paris Cedex 13)
- Department Name
- Service d’Hépato-Gastro-Entérologie
- Principal Investigator Name
- Marika Rudler
- Principal Investigator Email
- marika.rudler@aphp.fr
- Contact Person Name
- Marika Rudler
- Contact Person Email
- marika.rudler@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Bobigny)
- Department Name
- Hépatologie et Oncologie Hépatique
- Principal Investigator Name
- Pierre Nahon
- Principal Investigator Email
- pierre.nahon@aphp.fr
- Contact Person Name
- Pierre Nahon
- Contact Person Email
- pierre.nahon@aphp.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Service d’Hépato-gastro-entérologie
- Principal Investigator Name
- Laure Elkrief
- Principal Investigator Email
- l.elkrief@chu-tours.fr
- Contact Person Name
- Laure Elkrief
- Contact Person Email
- l.elkrief@chu-tours.fr
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Service d’Hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle
- Principal Investigator Name
- Jérome Gournay
- Principal Investigator Email
- jerome.gournay@chu-nantes.fr
- Contact Person Name
- Jérome Gournay
- Contact Person Email
- jerome.gournay@chu-nantes.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Service d’Hépato Gastro-entérologie
- Principal Investigator Name
- Ghassan RIACHI
- Principal Investigator Email
- ghassan.riachi@chu-rouen.fr
- Contact Person Name
- Ghassan RIACHI
- Contact Person Email
- ghassan.riachi@chu-rouen.fr
- Site Name
- CHRU De Nancy
- Department Name
- Service d’Hépatologie et de gastroentérologie
- Principal Investigator Name
- Vincent Haghnejad
- Principal Investigator Email
- v.haghnejad@chru-nancy.fr
- Contact Person Name
- Vincent Haghnejad
- Contact Person Email
- v.haghnejad@chru-nancy.fr
Sponsor
Primary sponsor
- Full Name
- Centre Hospitalier Universitaire De Lille
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Investigational products
- Investigational Product Name
- HIDONAC 5 g/25 ml, solution injectable pour perfusion
- Active Substance
- ACETYLCYSTEINE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS
- Route
- Intravenous
- Authorisation Status
- Marketing authorisation number: 34009 555 839 1 2 (France)
- Frequency
- Administered during day 1 to day 5 (intravenous infusion)
- Maximum Dose
- 300 mg/kg (maxDailyDoseAmount 300; doseUom mg/kg)
- Investigational Product Name
- Micronized Prednisolone
- Active Substance
- PREDNISOLONE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- EU MP PRD12675749 (product auth status present)
- Starting Dose
- 40 mg/day
- Dose Levels
- 40 mg/day (day 1-30); tapering from day 31 to day 60 in Arm 3: 40 mg/day (day 31-38), 30 mg/day (day 38-45), 20 mg/day (day 45-52), 10 mg/day (day 52-60)
- Frequency
- Once daily
- Maximum Dose
- 40 mg/day
- Dose Escalation Increase
- Initial 40 mg/day then 30 mg/day then 20 mg/day then 10 mg/day (tapering schedule in Arm 3)
- Investigational Product Name
- Placebo of Prednisolone 10mg
- Modality
- Other
- Combination Treatment
- Yes
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