PROlonged Corticosteroid Treatment or N-ACetylcysteine for Severe Alcoholic Hepatitis (PROCORNAC)

May 27, 2026 updated by: University Hospital, Lille

Only patients suffering from a severe form of alcoholic hepatitis (Maddrey's discriminant function greater than 32) require medical treatment. Oral prednisolone for 28 days is the only treatment which has been proven to improve short-term survival over placebo in patients with severe alcoholic hepatitis. However, prednisolone alone cannot be regarded as an ideal treatment because some patients still have a bad outcome despite being treated with corticosteroids. Response to treatment can be predicted by the Lille score, a simple tool that is calculated after 7 days of prednisolone course. The ideal binary cut-off of the Lille is 0.45, responders having a Lille score < 0.45 and non-responders having a Lille score ≥0.45. In terms of treatment management, approximately 30% of patients with severe alcoholic hepatitis do not take benefit from prednisolone and are classified as null responders by a Lille score greater than 0.56. In them, there is a consensus for stopping prednisolone after a 7-day course of treatment (Lille score is calculated after 7 days) while patients with a Lille score <0.56 continue treatment for a total of 30 days.

Numerous trials have attempted to test the impact of other strategies in association with prednisolone, but none of them has shown an improvement in survival (primary endpoint) as compared to prednisolone alone. These strategies include for instance pentoxifylline, amoxicillin-clavulanic acid and enteral nutrition.

Because oxidative stress is a major driver of liver injury during alcohol-related liver disease, antioxidants, especially N-acetylcysteine, have been tested for many years to treat alcoholic hepatitis. N-acetylcysteine alone does not seem to bring a survival benefit over placebo while it may improve outcome when combined to prednisolone.

Historically in severe alcoholic hepatitis, treatment is only given for one month. However, a significant proportion of patients still disclose impaired hepatic function after treatment has been stopped (e.g. 50% of patients still have a MELD score ≥17 after 60 days in). It is thus tempting to hypothesize that a proportion of patients will recover slowly and may take benefit from a prolonged treatment. Such strategy has been proposed in some old studies with relatively limited sample size but never tested with a rigorous approach.

In the present study, for the first time in alcoholic hepatitis, we will take into account the recent recommendations of international experts by choosing an innovative primary endpoint that does not only include mortality and evaluate this endpoint at the preferred timepoint of 90 days.

After more than 30 years of negative trials in severe alcoholic hepatitis, the present study is aimed to evaluate two important new strategies to decrease both mortality and liver impairment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
477

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NAC/Prednisolone/Placebo
N-acetylcysteine for five days (day 1 to day 5) in combination with prednisolone 40 mg/day for a total of 30 days, followed by a placebo for 30 additional days
Drug: N-Acetylcysteine (NAC) Treatment
N-acetylcysteine for five days (day 1 to day 5) at a daily dose of 300mg/Kg
Drug: Prednisolone
prednisolone 40 mg/day for a total of 30 days
Drug: Placebo of Prednisolone 10mg
Placebo of prednisolone 10mg for 30 additional days
Active Comparator: Placebo/Prednisolone/Placebo
Placebo for five days (day 1 to day 5) in combination with prednisolone 40 mg/day for a total of 30 days, followed by a placebo for 30 additional days
Drug: Prednisolone
prednisolone 40 mg/day for a total of 30 days
Drug: Placebo of N-acetylcysteine
Placebo of N-acetylcysteine for five days (day 1 to day 5)
Drug: Placebo of Prednisolone 10mg
Placebo of prednisolone 10mg for 30 additional days
Experimental: Placebo/Prednisolone/Prednisolone
Placebo for five days (day 1 to day 5) in combination with prednisolone 40 mg/day for a total of 30 days, followed by prednisolone (tapering dose) for 30 additional days
Drug: Prednisolone
prednisolone 40 mg/day for a total of 30 days
Drug: Placebo of N-acetylcysteine
Placebo of N-acetylcysteine for five days (day 1 to day 5)
Drug: Prednisolone 10mg
prednisolone 10mg (tapering dose) for 30 additional days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of patients alive with compensated liver disease
Time Frame: 90 days

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
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Lille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 22, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 25, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2024_0476
  • PHRC-23-0354 (Other Grant/Funding Number: DGOS, France)
  • 2025-522109-39-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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