Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
477
Countries
1
Sites
22
Alcoholic hepatitis
To assess the efficacy of the combination of N-acetylcysteine during 5 days with standard treatment by prednisolone (prednisolone during 30 days) or a prolonged treatment with prednisolone (during a total of 60 days) compared to standard treatment with prednisolone during 30 days to improve the rate of alive patients w…
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Lille
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 22 May 2026 → ongoing
- Decision date (initial)
- 2025-10-17
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- DGOS
External identifiers
- EU CT number
- 2025-522109-39-00
- ClinicalTrials.gov
- NCT06956482
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To assess the efficacy of the combination of N-acetylcysteine during 5 days with standard treatment by prednisolone (prednisolone during 30 days) or a prolonged treatment with prednisolone (during a total of 60 days) compared to standard treatment with prednisolone during 30 days to improve the rate of alive patients with compensated liver disease at 90 days.
Secondary objectives 3
- To assess the effect of combination of N-acetylcysteine infusion during 5 days associated with standard treatment with prednisolone (prednisolone during 30 days) or a prolonged treatment with prednisolone (during a total of 60 days) compared to standard treatment with prednisolone on: - the median and long term survival; - the rate of alive patients with compensated liver disease at 60, 180 and 360 days; - the incidence of infections and hepatorenal syndrome during 90 days.
- To assess the effect of combination of N-acetylcysteine injection during 5 days associated with standard treatment with prednisolone compared to standard treatment with prednisolone (by pooling the two arms standard treatment alone and prolonged treatment with prednisolone) on therapeutic response at day 7 and on the rate of alive patients with compensated liver disease at 30 days.
- To evaluate the safety of combination of N-acetylcysteine infusion during 5 days associated with standard treatment with prednisolone (prednisolone during 30 days) or a prolonged treatment with prednisolone (during a total of 60 days) compared to standard treatment with prednisolone.
Conditions and MedDRA coding
Alcoholic hepatitis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10001624 | Alcoholic hepatitis | 10019805 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Measures to Minimize Bias: Randomization and Blinding After informed consent and verification of inclusion and exclusion criteria, patients will be randomized and allocated in a 1:1:1 ratio to receive study drug or placebo. To ensure a centralized real-time randomization procedure, a web-based randomization will be performed using the electronic case-report form (eCRF) system by the investigator. The 1:1:1 assignment sequence (permutated blocks of variable size and the use of a computer random-number generator), stratified by center, will be produced by the sponsor and implemented in the eCRF. The randomization lists will not be disclosed to study centers, monitors, project statistician or to the project team.
The allocation to treatment will be performed as follows: when a participant is deemed eligible and ready for randomization, the electronic Case Report Form (eCRF) system will reveal the treatment kit number available at the clinical site. The corresponding kit number will be registered in the medical records, and the corresponding kit will exclusively be used to treat the patient. The kits will be prepared according to a computer-generated random list permuted with block-size. The allocation list and kit list will be aligned in the eCRF system to provide the patient with the allocated treatment. The eCRF will be programmed with blind-breaking instructions.
|
Randomised Controlled | Double | [{"id":148552,"code":2,"name":"Investigator"},{"id":148551,"code":3,"name":"Monitor"},{"id":148550,"code":1,"name":"Subject"}] | Arm 1: a. From day 1 to day 5: Prednisolone 40 mg/day (oral) + N-acetylcysteine (intravenous) b. From day 6 to day 30: Prednisolone 40 mg/day (oral) c. From day 31 to day 60: Placebo (oral) Arm 2: a. From day 1 to day 5: Prednisolone 40 mg/day (oral) + placebo (intravenous) b. From day 6 to day 30: Prednisolone 40 mg/day (oral) c. From day 31 to day 60: Placebo (oral) Arm 3: a. From day 1 to day 5: Prednisolone 40 mg/day (oral) + placebo (intravenous) b. From day 6 to day 30: Prednisolone 40 mg/day (oral) c. From day 31 to day 60: Prednisolone (oral) with tapering doses: - 40 mg/day from day 31 to day 38 - 30 mg/day from day 38 to day 45 - 20 mg/day from day 45 to day 52 - 10 mg/day from day 52 to day 60 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Patients aged 18-75
- Alcohol consumption of more than 40g/day (women) and 50g/day (men)
- Recent onset of jaundice (<3 months)
- Biopsy proven alcoholic hepatitis (transjugular liver biopsy)
- Maddrey’s discriminant function ≥ 32, defining severe alcoholic hepatitis
- MELD score ≥ 17
- Patients covered with social insurance
- Patients having provided written informed consent to participate
Exclusion criteria 14
- Hepatocellular carcinoma
- Uncontrolled gastrointestinal bleeding
- Previous severe allergy or hypersensitivity to N-acetylcysteine (anaphylactic shock, Quincke edema, severe urticaria)
- Hypersensitivity to any component of the medication
- MELD score <17
- Type 1 hepatorenal syndrome before the initiation of treatment
- Severe extrahepatic disease, with life expectancy < 6 months
- Any malignant tumor < 2 years (except skin carcinomas)
- Ongoing viral or parasitic infection
- Untreated bacterial infection. Patients on antibiotics to treat ongoing infection can be included if the investigator feels the sepsis is under control.
- Tuberculosis < 5 years
- Positive blood PCR in patients with positive antibodies against HCV
- Patient carrying HBV or HIV
- Treatment with corticosteroids, immunosuppression therapy or budesonide within 6 months before the study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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
Secondary endpoints 3
- - Overall survival at 90 and 360 days ; - Rate of patients alive with compensated liver disease defined by a MELD score <17 at 30-days, 60-days,180 and 360 days
- 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)
- - Cumulative incidence of infection within the first 90 days; - Cumulative incidence of hepatorenal syndrome within the first 90 days; - Serious adverse events within the first 90 days
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
HIDONAC 5 g/25 ml, solution injectable pour perfusion
PRD485693 · Product
- Active substance
- Acetylcysteine
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 300 mg/kg milligram(s)/kilogram
- Max total dose
- 300 mg/kg milligram(s)/kilogram
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- V03AB23 — ACETYLCYSTEINE
- Marketing authorisation
- 34009 555 839 1 2
- MA holder
- ZAMBON FRANCE S.A.
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The duration of the treatment has been extended to five days instead of 21 hours.
PRD12675749 · Product
- Active substance
- Prednisolone
- Substance synonyms
- (8S,9S,10S,11S,13S,14S,17R)-11,17-DIHYDROXY-17-(2-HYDROXYACETYL)-10,13-DIMETHYL-7,8,9,11,12,14,15,16-OCTAHYDRO-6H-CYCLOPENTA[A]PHENANTHREN-3-ONE, GLPG0303, DELTA-HYDROCORTISONE, 1,2-DEHYDROHYDROCORTISONE, METACORTANDRALONE
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- CENTRE HOSPITALIER REGIONAL ET UNIVERSITAIRE LILLE
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 2
Dextrose 5% + Normal saline solutions (10%)
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 1
SOLUPRED 20 mg, comprimé orodispersible
PRD10473252 · Product
- Active substance
- Prednisolone Metasulfobenzoate Sodium
- Pharmaceutical form
- ORODISPERSIBLE TABLET
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 30 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- 34009 349 368 7 6
- MA holder
- CHEPLAPHARM ARZNEIMITTEL GMBH
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Lille
- Sponsor organisation
- Centre Hospitalier Universitaire De Lille
- Address
- 2 Avenue Oscar Lambret, Cs 70001 Cs 70001
- City
- Lille Cedex
- Postcode
- 59037
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Lille
- Contact name
- Prof. Alexandre Louvet
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Lille
- Contact name
- Direction de la Recherche et l'Innovation
Locations
1 EU/EEA country · 22 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 477 | 22 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Poitiers
Service d’hépato-gastro-entérologie et assistance nutritive, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier Regional Universitaire De Tours
Service d’Hépato-gastro-entérologie, Avenue De La Republique, 37170, Chambray Les Tours
Centre Hospitalier Universitaire De Nantes
Service d’Hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Hospitalier Universitaire De Toulouse
Service d’Hépatologie, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9
Centre Hospitalier De Valenciennes
Service des Maladies de l'Appareil Digestif et de la Nutrition, 114 Avenue Desandrouin, 59300, Valenciennes
L’Hopital Alexandra Lepeve
Service d’Hépato Gastro-entérologie, 130 Avenue Louis Herbeaux, Cs 76367, Dunkirk Cedex 1
Centre Hospitalier Universitaire D'Angers
Service d’Hépato-gastro-entérologie, 4 Rue Larrey, 49100, Angers
Assistance Publique Hopitaux De Paris
Service d’Hépato-Gastro-Entérologie, 47 Boulevard De L Hopital, 75651, Paris Cedex 13
CHU Besancon
Service d’Hépatologie, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
Centre Hospitalier Universitaire De Caen Normandie
Service d’Hépato Gastro-entérologie, Avenue De La Cote De Nacre, Cs 30001, Caen Cedex 9
Assistance Publique Hopitaux De Paris
Hépatologie et Oncologie Hépatique, 125 Rue De Stalingrad, 93009, Bobigny Cedex
Centre Hospitalier Universitaire De Rennes
Service des Maladies de l'appareil digestif, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Universitaire Reims
Service d'Hépato-Gastro-Entérologie Digestive, 45 Rue Cognacq Jay, 51092, Reims Cedex
Centre Hospitalier Universitaire Grenoble Alpes
Service d’Hépato-gastro-entérologie, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
CHRU De Nancy
Service d’Hépatologie et de gastroentérologie, Rue Du Morvan, 54500, Vandoeuvre Les Nancy
Centre Hospitalier Universitaire Rouen
Service d’Hépato Gastro-entérologie, 1 Rue De Germont, Bp 96031, Rouen Cedex
Centre Hospitalier Universitaire De Dijon
Service d’Hépato-gastro-entérologie, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Universitaire De Lille
Service de Gastro-entérologie adultes – Maladies de l’appareil digestif, Rue Michel Polonovski, 59037, Lille Cedex
Hospices Civils De Lyon
Service Hépatologie et Addictologie, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04
Centre Hospitalier Universitaire De Nice
Pôle de Référence Hépatogastroentérologie et Oncologie Digestive, 151 Route De Saint Antoine, 06200, Nice
Assistance Publique Hopitaux De Paris
Service d'Hépatologie, 184 Rue Du Faubourg Saint Antoine, 75012, Paris
Centre Hospitalier Universitaire De Montpellier
Service d’Hépato-gastro-entérologie et Transplantation, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2026-05-22 | 2026-05-22 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2025-522109-398_Redacted | 1.2 |
| Protocol (for publication) | D1_Protocol signature 2025-522109-39 | 1.2 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS ans ICF patients_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS ans ICF trusted person_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Treatment notebook | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Hidonac | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Prednisolone 20mg | 1 |
| Synopsis of the protocol (for publication) | D1_French Protocol synopsis 2025-522109-39_Redacted | 1.1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2025-522109-39_Redacted | 1.1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-07-22 | France | Acceptable 2025-10-16
|
2025-10-17 |