Evaluation of Amoxicillin-Clavulanic Acid and Fluticasone Propionate Versus Placebo in Pediatric Patients with Protracted Cough: A Randomized, Double-Blind Trial

The primary objective of this randomized, double-blinded clinical trial is to evaluate the **efficacy** of two treatments compared to placebo in children with **protracted cough**. Specifically, the study aims to assess the effectiveness of **fluticasone propionate** inhalation in children with a prolonged dry cough without other findings suggestive of an underlying cough-related disease. Additionally, the trial seeks to determine the efficacy of oral **amoxicillin-clavulanic acid** in children with a prolonged productive cough, also without other indicative findings of an underlying disease. These objectives are clinically relevant as they aim to provide evidence-based treatment options for managing persistent cough in pediatric patients, potentially improving patient outcomes and reducing unnecessary medication use.

The clinical trial focuses on evaluating the efficacy of **fluticasone** inhalations and oral amoxicillin-clavulanic acid in children with **protracted cough**. The study population includes both male and female participants, specifically children aged 2 years and older. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific criteria, including a persistent cough lasting more than four weeks without any underlying medical diagnosis or symptoms suggestive of a background disease. Additionally, participants must not have a history of allergic reactions to the study medications and should not be concurrently enrolled in another clinical trial. The trial requires that parents of the participants have proficiency in the Finnish language and provide written informed consent for their child's participation. No specific lifestyle considerations such as diet or physical activity are mentioned for this study.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy of an **antibiotic** and an **inhaled corticosteroid** compared to a placebo in children with **protracted cough**. The trial will involve a comparison of **amoxicillin and clavulanic acid** administered orally and **fluticasone propionate** delivered via inhalation. The study is set to commence recruitment on September 1, 2025, and is expected to conclude by December 31, 2028. Participants will be involved in the study for a maximum treatment period of 8 weeks, depending on the intervention group they are assigned to.

The trial will begin with an inclusion (screening) visit, where potential participants will be assessed against the inclusion criteria, which include a persistent cough lasting more than four weeks without any underlying diagnosed condition or symptoms suggestive of a background disease. Participants must not have a history of allergic reactions to the study drugs and should not be enrolled in another clinical trial concurrently. Following successful screening, participants will be randomized into one of the study arms.

Study visits will be scheduled at regular intervals to monitor the participants' health and response to the treatment. These visits will include assessments of cough reduction, which is the primary endpoint, defined as a significant decrease in cough symptoms by at least 75% over three consecutive days. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted to evaluate the overall efficacy and safety of the interventions.

Participants may be withdrawn from the study early if they experience adverse reactions to the study medications, if they develop conditions that contraindicate continued participation, or if they choose to withdraw consent. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of several treatments to evaluate their efficacy in children with protracted cough. The **experimental medication** Amorion Comp is an oral suspension containing the active substances **amoxicillin** and **clavulanic acid**. It is formulated as a powder for oral suspension, with a concentration of 80 mg/ml. The medication is administered orally, with a maximum daily dose of 50 mg/kg and a maximum treatment period of 2 weeks. The product is manufactured by Orion Corporation and is identified by the EU medicinal product number PRD534022. Participant compliance with the dosing schedule will be monitored throughout the trial.

Another **experimental treatment** is Flixotide Evohaler, which contains the active substance **fluticasone propionate**. This medication is a pressurised inhalation suspension, delivered via inhalation. The maximum daily dose is 250 µg, with a total maximum dose of 14,000 µg over a treatment period of up to 8 weeks. The product is manufactured by GlaxoSmithKline Oy and is identified by the EU medicinal product number PRD390013. The administration of this inhaled corticosteroid will be closely monitored to ensure adherence to the prescribed dosing regimen.

The trial also includes the use of placebo treatments. The Evohaler- harjoitteluinhalaattori tilanjatkeella is a placebo inhaler device that does not contain any active substance. It is used to simulate the administration of an inhaled medication without delivering any pharmacologically active ingredients. Similarly, Syrspend oraaliliuos is a placebo oral solution, also devoid of active substances, used to mimic the administration of an oral medication. These placebo treatments are employed to maintain the double-blind nature of the trial and to serve as comparators for evaluating the efficacy of the experimental medications.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the significant reduction in cough symptoms. This is defined as either the cessation of cough or at least a 75% reduction in symptom scores compared to baseline, sustained over three consecutive days. The trial aims to compare the efficacy of an inhaled corticosteroid, **fluticasone propionate**, and an oral antibiotic, **amoxicillin and clavulanic acid**, against a placebo in children with protracted cough.