Evaluation of Inhaled Tobramycin and Colistimethate Sodium in Adult Bronchiectasis with Chronic Bronchial Infection: A Randomized Controlled Trial

The primary objective of the study is to evaluate the efficacy of **inhaled antibiotics** in reducing the colony-forming units in patients with **adult bronchiectasis** and chronic bronchial infection. This is assessed by comparing the outcomes of patients who receive inhaled antibiotics following a course of targeted oral or intravenous treatment to those in a placebo group. The clinical relevance of this objective lies in its potential to improve management strategies for chronic bronchial infections in bronchiectasis, thereby reducing bacterial load and potentially improving patient outcomes.

The clinical trial focuses on **adult bronchiectasis** and includes participants aged 20 to 90 years, comprising both male and female subjects. The study population is characterized by individuals who have experienced chronic bronchial infection and have undergone prior treatment. Participants are required to have a minimum of two sputum cultures positive for the same germ in the past year and must be under the care of the Multidisciplinary Bronchiectasis Unit of Hospital del Mar. The trial does not involve a vulnerable population. Participants' general health status is assessed based on the severity of bronchiectasis and exacerbations using current scales such as BSI, FACED, and EFACED. The trial includes individuals regardless of their background treatment, which may involve inhaled corticosteroids, bronchodilators, oral antibiotics like azithromycin, and respiratory physiotherapy. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **inhaled antibiotics** in reducing colony-forming units in patients with **adult bronchiectasis** and chronic bronchial infection. This is a randomized, double-blind, placebo-controlled trial, categorized as a Phase 4 study. The trial will involve the administration of **tobramycin** and **colistimethate sodium** as nebulizer solutions, with a maximum treatment period of 48 weeks. The study is expected to commence recruitment on May 2, 2024, and conclude by March 1, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (20 to 90 years), diagnosis of bronchiectasis, and history of positive sputum cultures. Following the screening, eligible participants will be randomized to receive either the active treatment or placebo. The trial will include regular follow-up visits to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The primary endpoint is the reduction in the number of colony-forming units, which will be assessed at these visits. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted.

Participant involvement is expected to last for the entire 48-week treatment period, with conditions for early termination including non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events. The trial is designed to ensure that all procedures align with standard clinical practices, minimizing additional risks to participants. The study aims to provide evidence-based insights into the effectiveness of inhaled antibiotics in managing chronic bronchial infections in patients with bronchiectasis.

The clinical trial involves the administration of **TOBRAMYCIN**, an antibiotic formulated as a nebuliser solution. The active substance, tobramycin, is of chemical origin. The medication is administered via **inhalation**. The maximum daily dose is 600 mg, with a total maximum dose of 600 mg over the treatment period. The treatment duration is set for a maximum of 48 weeks. The trial aims to assess the efficacy of inhaled tobramycin in reducing colony-forming units in patients with chronic bronchial infection.

Another experimental medication used in the trial is **COLISTIMETHATE SODIUM**, also an antibiotic in the form of a nebuliser solution. The active substance, colistimethate sodium, is chemically derived. This medication is administered through inhalation, with a maximum daily dose of 4,000,000 IU and a total maximum dose of 4,000,000 IU over the treatment period. The treatment period is similarly capped at 48 weeks. The study evaluates the impact of inhaled colistimethate sodium on chronic bronchial infections.

The trial also includes the use of a non-experimental treatment, **Suero Fisiológico Braun 0.9%**, which serves as a placebo. This solution is used as a parenteral solvent and contains sodium chloride. The placebo is employed to provide a comparative baseline for evaluating the effectiveness of the experimental antibiotics. The administration details for the placebo are not specified in the trial data.

The efficacy of the clinical trial titled "Pharmacological Strategies of Inhaled Antibiotherapy in Bronchiectasis with Chronic Bronchial Infection: BRONCHIPHARMA Study" will be assessed by evaluating the primary endpoint, which is the reduction in the number of **colony-forming units (CFU)**. This endpoint will be used to determine the effectiveness of inhaled antibiotics in patients with chronic bronchial infection who have previously received a course of targeted oral or intravenous treatment. The trial aims to compare the CFU reduction in the treatment group against a placebo group.