Efficacy of Methylprednisolone Acetate and N-Acetylcysteine in Severe Acute Alcoholic Hepatitis: A Randomized Controlled Trial

The primary objective of this study is to assess the **efficacy** of the combination of methylprednisolone and N-acetylcysteine (NAC) in reducing one-month mortality in patients with severe acute alcoholic hepatitis. This is clinically relevant as severe acute alcoholic hepatitis is associated with high mortality rates, and improving survival outcomes is a critical goal in the management of this condition.

Secondary objectives include:

• Assessing mortality at three and six months.
• Evaluating liver complications, infections, and renal failure.
• Assessing the tolerance to N-acetylcysteine.
• Examining the relationship between the Lille index at day 7 and the response to treatment.

The clinical trial focuses on patients diagnosed with **acute alcoholic hepatitis**. The study population includes both males and females, aged between 18 and 75 years, who have been diagnosed according to AASLD guidelines or have compatible liver histology. Participants are required to have a Maddrey Score of 32 or higher. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' willingness to participate is confirmed through written informed consent. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed to evaluate the efficacy of **methylprednisolone** combined with **N-acetylcysteine** (NAC) in patients diagnosed with severe acute alcoholic hepatitis, characterized by a Maddrey score of 32 or higher. This is a phase III, randomized, double-blind, controlled trial aimed at assessing the primary endpoint of one-month mortality. Secondary endpoints include mortality at three and six months, liver complications, infections, renal failure, tolerance to NAC, and the relationship between the Lille index at day 7 and treatment response. The trial is expected to run from September 2022 to December 2025.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (18-75 years), diagnosis per AASLD guidelines, and informed consent. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and to collect data on the endpoints. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the outcomes.

The expected duration of participant involvement is up to one month, with the possibility of early termination if adverse events occur, if the participant withdraws consent, or if the investigator deems it necessary for the participant's safety. The trial will utilize intravenous perfusion for the administration of the study drugs, with a maximum daily dose of 32 mg for methylprednisolone and 150 mg/kg for NAC. The trial's methodology ensures rigorous data collection and analysis to determine the treatment's efficacy and safety in the specified patient population.

The clinical trial involves the administration of **methylprednisolone acetate** in combination with **lidocaine hydrochloride monohydrate**. Methylprednisolone acetate is a glucocorticoid with the ATC code H02AB04, and it is administered in the form of an intravenous perfusion. The pharmaceutical form is designated as PHF00243MIG. The maximum daily dose of methylprednisolone acetate is 32 mg, with a total maximum dose of 224 mg over the treatment period. The treatment period is limited to one day. Lidocaine hydrochloride monohydrate is included as an active substance in the formulation, although its specific role in the trial is not detailed separately from methylprednisolone acetate.

**Acetylcysteine** is also utilized in this trial, serving as an antidote with the ATC code V03AB23. It is administered via intravenous perfusion, with the pharmaceutical form identified as PHF00169MIG. The maximum daily dose for acetylcysteine is 150 mg/kg, and the total maximum dose is also 150 mg/kg, administered over a single day. Acetylcysteine is known by several synonyms, including N-acetylcysteine and N-acetyl-L-cysteine. The trial aims to evaluate the efficacy of the combination of methylprednisolone and acetylcysteine in reducing one-month mortality in patients with severe alcoholic hepatitis.

Both medications are administered intravenously, and the trial does not include any pediatric formulations. The study does not involve any orphan drug designations. Participant compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol. The trial does not utilize any placebo or comparator treatments, focusing solely on the experimental combination of methylprednisolone and acetylcysteine.

The efficacy of the treatment in this clinical trial will be assessed primarily by evaluating the **1-month mortality** rate in patients with Severe Acute Alcoholic Hepatitis. This primary endpoint will determine the effectiveness of the combination of methylprednisolone and N-acetylcysteine (NAC) in reducing mortality within the first month of treatment. Secondary endpoints include assessing mortality at three and six months, evaluating liver complications, infections, renal failure, and the tolerance to NAC. Additionally, the relationship between the Lille index at day 7 and the response to treatment will be analyzed.