Efficacy of Betamethasone Sodium Phosphate in Pediatric Symptomatic Adenovirus Infection: A Double-Blind, Randomized, Placebo-Controlled Trial

The primary objective of this double-blind randomized controlled study is to evaluate the **efficacy** of mono-administration of betamethasone, in addition to standard antipyretic therapy (paracetamol or ibuprofen), in children with febrile **adenovirus infection**. The study aims to increase the proportion of children who are afebrile within 24 hours of administration. This is clinically relevant as it addresses the rapid alleviation of fever, a common and distressing symptom in pediatric adenovirus infections, potentially improving patient comfort and reducing the risk of complications associated with prolonged fever.

Secondary objectives include:

• Reduction of pharyngeal tonsil pain
• Reduction of the incidence and duration of hospitalization
• Reduction of the overall duration of fever

These secondary objectives are significant as they aim to enhance the overall management of adenovirus infections by minimizing pain, reducing healthcare resource utilization, and further decreasing the duration of fever, thereby potentially improving patient outcomes and quality of life.

The clinical trial focuses on evaluating the efficacy of **betamethasone** mono-administration in children with febrile adenoviral infection. The study population comprises both male and female participants, aged between 6 months and 6 years, with a body weight ranging from 5 to 27 kg. Participants are required to have a body temperature greater than 37.5°C, measured with an axillary or ear thermometer, persisting for a minimum of 6 hours to a maximum of 5 days. The trial includes children with a clinical picture compatible with pharyngo-tonsillar infection due to **adenovirus**, exhibiting symptoms such as pharyngodynia, asthenia, hyporexia, nausea, vomiting, diarrhea, cough, rhinitis, abdominal pain, or otalgia, and signs like pharyngeal hyperemia, airway inflammation, lymphadenopathy, or skin rash. A positive antigenic swab for adenovirus is required, and a negative swab for SBEGA is necessary if deemed appropriate. The trial involves a vulnerable population, and informed consent must be obtained from the parents or guardians. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of mono-administration of **betamethasone** in children with symptomatic **adenovirus infection**. The trial aims to assess the effectiveness of betamethasone in addition to standard antipyretic therapy, such as paracetamol or ibuprofen, in increasing the proportion of children without fever within 24 hours of administration. The study will involve participants aged between 6 months and 6 years, with a body weight ranging from 5 to 27 kg, who present with a body temperature greater than 37.5°C and clinical symptoms compatible with pharyngo-tonsillar infection due to adenovirus.

The trial will commence with a screening visit to confirm eligibility based on inclusion criteria, including a positive antigenic swab for adenovirus and a negative swab for SBEGA if necessary. Following randomization, participants will receive either the test product, BENTELAN 0.5 mg effervescent tablets, or a placebo, both administered orally. The primary endpoint is the proportion of patients achieving a body temperature below 37.5°C between 18 and 24 hours post-randomization. Secondary endpoints include the level of pharyngo-tonsillar pain, the proportion of children requiring hospitalization, and the duration of fever.

Participants will be involved in the study for a maximum treatment period of one day, with follow-up visits scheduled to monitor outcomes and adverse events. The trial is expected to start recruitment on March 15, 2024, and conclude by June 1, 2025. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The study is categorized as a Phase III clinical trial, indicating its focus on efficacy and safety in a larger patient population.

The clinical trial involves the administration of **BENTELAN 0.5 mg effervescent tablets**, which contain the active substance **betamethasone sodium phosphate**. This medication is provided in the form of effervescent tablets and is intended for **oral use**. The dosage is calculated based on body weight, with a maximum daily dose of 0.2 mg/kg. The treatment period is limited to a maximum of one day. The primary objective of the study is to evaluate the efficacy of betamethasone in children with symptomatic adenovirus infection, specifically in reducing fever within 24 hours of administration. Compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the medication's efficacy.

In addition to the experimental medication, the study utilizes **Aqua ad iniectabilia Braun**, a solvent for parenteral use, which contains **water for injection**. This product is also administered orally, with a maximum daily dose of 20 ml. It serves as a placebo in the trial, allowing for a double-blind randomized controlled study design. The placebo is used to compare the effects of the active treatment against a non-active substance, ensuring the reliability of the study results. The administration of the placebo follows the same schedule as the experimental medication, and participant compliance is similarly monitored to maintain the integrity of the trial data.

Standard-of-care therapy, including antipyretic treatments such as paracetamol or ibuprofen, is permitted alongside the trial medications. This ensures that participants receive appropriate care for their condition while allowing the study to focus on the additional benefits of betamethasone administration. The trial is designed to assess the mono-administration of betamethasone in conjunction with standard antipyretic therapy, aiming to increase the proportion of children without fever within the specified timeframe.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the proportion of patients with persistent resolution of fever, defined as a body temperature below 37.5°C, measured 18 and 24 hours after randomization. This will determine the effectiveness of **betamethasone** mono-administration in children with symptomatic adenovirus infection in achieving fever resolution within 24 hours.

Secondary endpoints include the level of pharyngo-tonsillar pain, which will be measured using the FLACC scale for children aged 6 to 35 months and the Faces Pain Rating Scale (Wong-Baker Scale) for children aged 36 months to 6 years. Additional secondary endpoints are the proportion of children requiring hospitalization, the length of hospitalization in days for those hospitalized, the cumulative incidence of fever resolution from randomization until the first confirmed body temperature below 37.5°C, and the duration of fever from randomization until the last body temperature measurement above 37.5°C.

Data collection will involve the use of validated scales and thermometers to ensure accurate and reliable measurements. The trial is designed to provide a comprehensive assessment of the efficacy of betamethasone in conjunction with standard antipyretic therapy in managing febrile adenoviral infections in the pediatric population.