Efficacy and Safety of Buccalin Tablets in Preventing Recurrent Lower Respiratory Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to **confirm** and collect additional clinical data on the efficacy and safety of Buccalin® tablets in the prophylaxis of **Recurrent Lower Respiratory Tract Infections (RLRTIs)**. This is clinically relevant as RLRTIs are a significant health concern, often leading to increased morbidity and healthcare utilization. By evaluating Buccalin® tablets, the study aims to provide evidence on their potential to reduce the incidence of these infections, thereby improving patient outcomes and reducing the burden on healthcare systems.

The clinical trial involves a total of **24 participants** who are being studied to confirm and collect more clinical data on the use of Buccalin tablets in the prophylaxis of **Recurrent Lower Respiratory Tract Infections (RLRTIs)**. The study population includes both male and female subjects, ranging in age from 18 to 99 years, encompassing adults and older adults. Participants were selected based on their history of recurrent lower respiratory tract infections, defined as having two or more episodes of respiratory tract infections within the 12 months prior to the run-in phase and during the run-in phase. These infections include acute bronchitis and exacerbations of chronic lung diseases such as asthma, COPD, and bronchiectasis. The trial does not include a vulnerable population, and participants are required to have RLRTIs documented by appropriate microbiological diagnostic tests. Additionally, participants are those who have not received vaccinations for pertussis, COVID-19, respiratory syncytial virus, influenza, or pneumococcal infections. The selection criteria ensure that participants are willing and able to provide informed consent and adhere to protocol requirements.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study with two arms, conducted across multiple centers. The primary objective is to confirm and gather additional clinical data on the efficacy and safety of Buccalin tablets in the prophylaxis of **recurrent lower respiratory tract infections (RLRTIs)**. The trial is set to commence recruitment on November 15, 2024, and is expected to conclude by May 15, 2028. Participants will be randomly assigned to receive either the active treatment, Buccalin, or a placebo, both administered in the form of gastro-resistant tablets via oral use.

The study will involve several key visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age (18 to 99 years), history of recurrent LRTIs, and vaccination status. Following successful screening, participants will enter the treatment phase, which spans 12 months. During this period, follow-up visits will be scheduled at 3, 6, and 9 months to monitor the reduction in infection episodes, duration of RLRTIs, and the number of antibiotic treatments required. Participants will also complete a Visual Analogue Scale (VAS) to assess their condition.

The end-of-study visit will occur at the conclusion of the 12-month treatment period, where final assessments will be conducted to evaluate the primary endpoint of infection episode reduction and secondary endpoints, including safety evaluations through adverse event reporting. Participant involvement is expected to last approximately 12 months, with conditions for early termination including withdrawal of consent, non-compliance with protocol requirements, or adverse events that necessitate discontinuation. The trial aims to provide robust data on the prophylactic use of Buccalin in managing RLRTIs, contributing to the understanding of its clinical benefits and safety profile.

The clinical trial involves the administration of **Buccalin**, a gastro-resistant tablet formulated for oral use. Buccalin contains active substances including **Streptococcus agalactiae**, **Haemophilus influenzae**, **Staphylococcus aureus**, and **Streptococcus pneumoniae**. These substances are classified under the ATC code J07AX, indicating their categorization as other bacterial vaccines. The pharmaceutical form of Buccalin is a gastro-resistant tablet, designed to withstand gastric acidity and ensure the release of active ingredients in the intestine. The maximum daily dose is 31.5 billion organisms, with a total maximum dose of 378 billion organisms over a treatment period of up to 12 weeks. Buccalin is manufactured by Laboratorio Farmaceutico S.I.T. S.R.L. in Italy.

The trial also includes a **placebo** group, where participants receive seven gastro-resistant tablets containing only excipients. The placebo tablets are composed of lactose, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate, eudragit L 100-55, sodium hydroxide, talc, triethyl citrate, titanium dioxide, iron oxide red, iron oxide yellow, iron oxide black, and opaglos. These tablets are designed to mimic the appearance and administration route of the active treatment without containing any active pharmaceutical ingredients. The placebo serves as a control to assess the efficacy and safety of Buccalin in the prophylaxis of recurrent lower respiratory tract infections.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the reduction in the number of infection episodes during the 12-month treatment period in the Buccalin® group compared to the placebo group. Secondary endpoints include the reduction in the number of infection episodes at 3, 6, and 9 months of treatment, the mean duration in days per **Recurrent Lower Respiratory Tract Infection (RLRTI)** during both the treatment and follow-up periods, and the number of antibiotic treatments required for respiratory events during these periods. Additionally, the number of sick days for patients or caregivers will be evaluated.

Patient-reported outcomes will be collected using a Visual Analogue Scale (VAS) ranging from 0 (the worst situation) to 10 (the best situation) during the treatment period. Safety will be quantitatively and qualitatively evaluated in terms of adverse events reported. These efficacy parameters will be measured and collected at specified intervals throughout the trial, ensuring a comprehensive analysis of the treatment's impact on RLRTIs. The trial is designed to confirm and gather more clinical data on the efficacy of Buccalin® tablets in the prophylaxis of RLRTIs, with a focus on both the reduction of infection episodes and the overall improvement in patient health outcomes.