Non-Inferiority Randomized Controlled Trial of Short vs. Standard Amoxicillin Sodium Course in Adults with Lower Limb Erysipelas

The primary objective of this study is to demonstrate that a short course of **amoxicillin** (5 days, 50 mg/kg) is not inferior to the standard 10-day course in achieving complete remission of erysipelas in adults diagnosed with lower limb erysipelas by day 12 ± 2. This is clinically relevant as it could potentially reduce the duration of antibiotic therapy, minimizing side effects and resistance development while maintaining therapeutic efficacy.

Secondary objectives include:

• Comparing the rate of clinical remission, defined by the disappearance of fever and symptoms such as pain, warmth, tenderness, erythema, and edema, with a clinical severity score of ≤1.
• Assessing the rate and number of patients who do not require additional antibiotherapy for cellulitis.
• Evaluating the rate of recurrence by day 28 ± 2.
• Comparing the rate of adverse events between the two treatment strategies.
• Determining the rate of complete remission by day 7 ± 2, characterized by symptom resolution and absence of additional antibiotherapy.

The clinical trial involves **adults diagnosed with lower limbs erysipelas**. The study population includes both male and female participants aged 18 years and older. Participants are required to be in general good health, with specific inclusion criteria such as the absence of cutaneous necrosis, crepitations, blisters, and solid purpura. They must also be affiliated with a social security scheme and have provided written consent. The trial does not involve a vulnerable population. Participants are selected based on clinical signs of leg erysipelas present for 5 days or less, characterized by warmth, erythema, edema, and/or pain, along with a severity score of 3 or more. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of a short course of **amoxicillin sodium** compared to the standard course in treating adults diagnosed with lower limb erysipelas. This study is a non-inferiority, randomized, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus maintaining a double-blind methodology. The trial is expected to commence on January 28, 2025, and conclude by February 28, 2028, with the primary objective of demonstrating that a 5-day course of amoxicillin is not inferior to a 10-day course in achieving complete remission by day 12, as confirmed by a central independent committee.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (≥18 years), absence of cutaneous necrosis, and clinical signs of erysipelas. Following the inclusion visit, participants will be randomized to receive either the short or standard course of treatment. Follow-up visits will be scheduled to monitor the rate of complete remission, defined by the disappearance of fever, pain, warmth, tenderness, erythema, and edema, and the absence of additional antibiotic therapy. The end-of-study visit will assess the primary and secondary endpoints, including the rate of recurrence and adverse events.

The expected duration of participant involvement is approximately 28 days, with conditions for early termination including the development of severe adverse events or the need for additional antibiotic therapy. The trial will adhere to rigorous scientific standards to ensure the reliability and validity of the results, contributing valuable data to the understanding of optimal treatment durations for erysipelas.

The clinical trial involves the administration of **amoxicillin sodium**, a semi-synthetic penicillin antibiotic, as the experimental medication. The pharmaceutical form of the medication is designated as PHF00231MIG. The medication is administered orally, with a maximum daily dose of 5 grams and a total maximum dose of 50 grams over the treatment period. The trial compares a short course of 5 days to a standard course of 10 days, with the objective of demonstrating non-inferiority in achieving complete remission of erysipelas. The dosing schedule is designed to ensure that participants receive the appropriate amount of medication to evaluate the efficacy of the shorter treatment duration.

In this study, no non-experimental treatments such as placebo or comparator treatments are utilized. The focus is solely on the administration of amoxicillin sodium to assess its effectiveness in treating erysipelas. Participant compliance with the dosing regimen is monitored to ensure adherence to the prescribed treatment schedule. The trial's design includes blinded adjudication by a central independent committee, which evaluates the clinical outcomes using photographs and clinical data to confirm remission of erysipelas.

Efficacy in this clinical trial will be assessed primarily through the **rate of complete remission** at day 12 ± 2. Complete remission is defined as the disappearance of fever (temperature ≥ 38°C) and the resolution of pain, warmth, tenderness, erythema, and edema at the site of erysipelas. Additionally, for the cutaneous plaque, a clinical severity score of less than or equal to 1 is required, along with the absence of additional antibiotic therapy for cellulitis.

Secondary endpoints include the rate of clinical remission, which involves the same criteria as complete remission but is assessed at day 12 ± 2 and day 7 ± 2. Other secondary endpoints are the rate and number of patients not receiving additional antibiotic therapy at day 12 ± 2, the rate of recurrence defined by the need for additional antibiotic therapy for cellulitis between day 12 and day 28 ± 2, and the rate of adverse events during the treatment and follow-up periods as reported by the patient.

The trial aims to demonstrate that a short course (5 days) of amoxicillin 50 mg/kg is not inferior to the usual course (10 days) in achieving complete erysipelas remission. Efficacy assessments will be confirmed by a central independent committee, blinded to the intervention received, using photos and clinical data.