Evaluation of Inhaled Levofloxacin and Sodium Chloride in Community-Acquired Pneumonia Patients With and Without Pre-Existing Lung Disease

The primary objective of this study is to evaluate the impact of adding inhaled **levofloxacin** 240 mg, administered twice daily for three days, on the physiological and infectious status of patients with **community-acquired pneumonia** (CAP), both with and without pre-existing lung disease. This investigation is clinically relevant as it aims to determine whether this treatment approach can enhance patient outcomes by improving infection control and physiological parameters in CAP, a common and potentially severe respiratory condition. No secondary objectives are specified for this study.

The clinical trial focuses on patients diagnosed with **community-acquired pneumonia**. The study population includes both male and female participants aged 18 years and older. Participants are required to have been admitted to the hospital within 24 hours and present with a radiologically confirmed new-onset chest infiltrate consistent with pneumonia, accompanied by symptoms such as fever, cough, sputum production, dyspnea, and/or chest pain. The trial does not target a vulnerable population. Participants must be able to provide informed consent. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific clinical criteria, including treatment with certain antibiotics and elevated C-reactive protein levels or central body temperature. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the effects of **levofloxacin** 240 mg nebuliser solution, administered via inhalation, on patients with community-acquired pneumonia. This study is a randomized, double-blind, controlled trial, conducted over a period of three days. The trial aims to assess whether the addition of inhaled levofloxacin to standard treatment improves or worsens physiological or infectious status in patients with and without pre-existing lung disease. The trial is set to begin recruitment in November 2024 and is expected to conclude by November 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as hospital admission within 24 hours, new-onset chest infiltrate consistent with pneumonia, and specific treatment regimens. The primary endpoint is the proportion of patients experiencing a drop in FEV1 of 20% or 300mL one hour after the first inhalation. Secondary endpoints include changes in FEV1 from baseline to day 4, CRP levels, and patient-reported outcomes related to dyspnoea, cough, and fatigue.

The expected length of participant involvement is three days, with follow-up visits occurring daily to monitor physiological and infectious parameters. The end-of-study visit will coincide with the completion of the treatment period or discharge, whichever comes first. Conditions that may lead to early termination from the study include significant adverse reactions or withdrawal of consent. The trial will utilize a placebo control, with sodium chloride nebuliser solution serving as the comparator. The study is categorized as a Phase 4 trial, exploring the therapeutic and safety-related effects of an approved medication in a new patient population.

The clinical trial involves the administration of **Quinsair 240 mg nebuliser solution**, which contains the active substance **levofloxacin**. This experimental medication is formulated as a nebuliser solution and is administered via **inhalation**. The dosage regimen for this trial is 240 mg of levofloxacin, administered twice daily for a maximum treatment period of three days. The total maximum daily dose is 480 mg, with a cumulative maximum dose of 1440 mg over the treatment period. Levofloxacin is a chemical-origin antibiotic, and its administration is intended to assess its impact on the physiological and infectious status of patients with community-acquired pneumonia (CAP), both with and without pre-existing lung disease. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to the experimental treatment, the study utilizes **Sodium Chloride** as a non-experimental treatment. Sodium chloride is also provided in the form of a nebuliser solution and is administered via inhalation. The role of sodium chloride in this trial is as a comparator treatment. The maximum daily dose of sodium chloride is 5 ml, with a total maximum dose of 15 ml over the three-day treatment period. Sodium chloride serves as a saline solution, and its use in the trial is to provide a baseline for evaluating the effects of the experimental medication. Compliance with the administration of sodium chloride will also be monitored to ensure adherence to the study protocol.

Efficacy in the clinical trial titled "Local Antibiotic Delivery for Community Acquired Pneumonia - Pilot study (LANDCAP1)" will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients experiencing a drop in **FEV1** (Forced Expiratory Volume in 1 second) of 20% or 300 mL one hour following the first inhalation of the study medication. Secondary endpoints include the proportion of patients with a drop in FEV1 of 20% or 300 mL from baseline to day 4 or discharge, whichever occurs first. Additional secondary endpoints involve measurements such as C-reactive protein (CRP) levels on day 4 compared to days 1 to 3, mean arterial pressure (MAP) ≤ 65, respiratory frequency > 25, pulse > 100, or the need for supplemental oxygen on day 4. Procalcitonin (PCT) levels on day 4 higher than baseline, and temperature ≥ 38.0 °C on day 4 are also evaluated. Patient-reported outcomes will be assessed through changes in Visual Analogue Scales for dyspnoea, cough, and fatigue from baseline to day 4.