Evaluation of Amoxicillin Trihydrate Regimen Duration in Pediatric Community-Acquired Alveolar Pneumonia: A Randomized Non-Inferiority Trial

The primary objective of this clinical trial is to evaluate the **non-inferiority** of a shortened antibiotic treatment strategy using **amoxicillin** at a dosage of 80-100 mg/kg/day for 3 days in cases of rapid response, or 5 days in cases of delayed response, compared to a standard treatment duration of 5 days for rapid response or 7 days for delayed response. This is specifically for the management of non-severe community-acquired alveolar pneumonia in children aged 3 to 59 months. The primary endpoint is the rate of treatment failure at 7 days, which is clinically relevant as it may allow for reduced antibiotic exposure without compromising treatment efficacy.

Secondary objectives include:

• Comparing the two antibiotic therapy strategies in terms of the rate of therapeutic failure at 30 days of antibiotic therapy.
• Assessing the occurrence of adverse drug effects up to 30 days between the two strategies.
• Evaluating compliance throughout the duration of antibiotic therapy with amoxicillin.
• Comparing the duration of antibiotic therapy between the two strategies.

The clinical trial focuses on children diagnosed with **community-acquired alveolar pneumonia**, specifically targeting a pediatric population aged between 3 and 59 months. Both male and female subjects are included, and the study acknowledges the involvement of a vulnerable population due to the young age of participants. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants were selected based on specific inclusion criteria, including a recent diagnosis of community-acquired alveolar pneumonia characterized by a combination of major and minor clinical criteria, such as fever, polypnea, and specific findings on chest X-ray, among others. The study population is required to have experienced the onset of symptoms less than 7 days prior to inclusion and must not meet any criteria for hospitalization. The trial does not specify any particular lifestyle considerations such as diet or physical activity for the participants.

The clinical trial is designed to evaluate a therapeutic strategy for reducing the duration of **antibiotic** therapy in children with community-acquired alveolar pneumonia. This study is a randomized, controlled, non-inferiority trial aimed at demonstrating the non-inferiority of a shorter antibiotic treatment regimen using **amoxicillin trihydrate**. The trial will compare a 3-day treatment for rapid responders and a 5-day treatment for delayed responders against a standard 5-day treatment for rapid responders and a 7-day treatment for delayed responders. The primary endpoint is the rate of therapeutic failure at day 7, defined by the necessity to change antibiotic therapy due to unsatisfactory clinical response, clinical deterioration, or the need for hospitalization or continuation of therapy beyond day 7.

The trial will commence with a screening visit to confirm eligibility, which includes children aged 3 to 59 months with a diagnosis of community-acquired alveolar pneumonia, characterized by specific clinical criteria. Following the screening, participants will be randomized into one of the treatment arms. The study will involve follow-up visits on day 7 and day 30 to assess the primary and secondary endpoints, including therapeutic failure rates, adverse effects, compliance, and duration of antibiotic therapy. The end-of-study visit will occur on day 30, marking the conclusion of participant involvement.

The expected duration of participant involvement is up to 30 days, with the possibility of early termination if criteria for therapeutic failure are met, such as clinical deterioration or the need for hospitalization. The trial is anticipated to start recruitment in September 2024 and is estimated to conclude by May 2027. The study will utilize oral administration of amoxicillin trihydrate, with a maximum daily dose of 100 mg/kg and a total maximum dose of 700 mg/kg over the treatment period. The trial is not categorized as low intervention and is conducted under phase 5, with a focus on evaluating a shorter treatment duration than current recommendations. Participants will be monitored for compliance and adverse effects throughout the study duration.

The clinical trial involves the use of **Amoxicillin Trihydrate**, a **chemical** active substance, as the experimental medication. The pharmaceutical form of this medication is a **powder for oral solution**, specifically designed for oral administration. The dosing regimen for **Amoxicillin Trihydrate** is determined based on the participant's body weight, with a dosage range of 80-100 mg/kg/day. The treatment duration is contingent upon the patient's response: 3 days for a rapid response and 5 days for a delayed response. The maximum daily dose is capped at 100 mg/kg, with a total maximum dose of 700 mg/kg over a treatment period not exceeding 7 days. The administration of the medication is facilitated by devices such as a dropper assembly and a 5 mL oral dispenser, both of which are CE marked and ensure accurate dosing for pediatric patients.

In this trial, **Amoxicillin Trihydrate** serves as a **β-lactam bactericidal antibiotic**, targeting non-severe community-acquired alveolar pneumonia in children aged 3 to 59 months. The trial aims to evaluate the non-inferiority of a shorter antibiotic treatment strategy compared to the standard duration. No non-experimental treatments, such as placebo or comparator treatments, are utilized in this study. Participant compliance with the dosing schedule is monitored through the use of the aforementioned devices, ensuring precise delivery of the medication. The trial does not involve any orphan drug designation or pediatric-specific formulation of the medication.

Efficacy in this clinical trial will be assessed by evaluating the rate of therapeutic failure in children with non-severe community-acquired alveolar pneumonia. The primary endpoint is the rate of therapeutic failure on day 7 (D7), which is defined by several criteria: a change in antibiotic therapy necessary before D7 due to a lack of satisfactory clinical response or clinical deterioration of the pneumonia, a decision to resume or continue antibiotic therapy after D7 in connection with the pneumonia, and hospitalization or death due to clinical deterioration related to community-acquired pneumonia.

Secondary endpoints include the therapeutic failure rate on Day 30 (D30), which encompasses hospitalization linked to the initial episode, an abnormal check-up chest x-ray at 1 month with persistent pneumonia, the occurrence of complications such as severe sepsis, pleurisy, or pulmonary sequelae, and relapse defined by the development of signs of pneumonia 6 to 14 days after the respiratory rate returns to normal. Additionally, adverse effects attributable to antibiotics during and after taking **amoxicillin**, compliance throughout the duration of antibiotic therapy, and the duration of antibiotic therapy collected at visits on D7 and D30 will be assessed.