An Open-label, Multicenter, Parallel-group Randomized Clinical Trial Assessing Non-inferiority of Inhaled Lexofloxacin vs Usual Care for Treatment of Community-Acquired Pneumonia

Community-acquired pneumonia is common and potentially fatal. Standard-of-care treatment mainly consists of systemic antibiotics and treatment supporting recovery (e.g. oxygen-therapy, fluid rescucitation, respiratory physiotherapy, sufficient dietary intake etc.). As with all medicinal treatments, antibiotic treatment is hard on the body and can lead to side-effects as well as organ-failure in extreme cases.

Antibiotic treatment naturally promotes antimicrobial resistance (AMR), which result in less effective antibiotic treatment, and ultimately it could potentially lead to antibiotics being rendered useless in treating infections such as pneumonia.

A strategy to reduce the promotion of antimicrobial restistance (AMR) is better targeting of the disease-inducing microbes and several other strategies exists. Physicians and researchers usually categorize the targeting of disease-promoting microbes as either "local"/"topical" or "systemic". No "local" treatment of community-acquired pneumonia has been demonstrated to this day, but "local" treatment is theoretically possible with inhaled antibiotics. This treatment strategy has been hypothesized in the last decade, but no studies have been conducted regarding community-acquired pneumonia.

This study will include 460 patients and be conducted in two stages: Stage A and Stage B, each stage including 230 patients.

Patients are included voluntarilty and with prior written informed consent.

Patients included in stage A will be treated with systemic antibiotics for 24 hours and will then be randomized to further treatment with either inhaled levofloxacin 240mg twice daily or continue the "usual care"-treatment that they were receiving. The duration of intervention is up to 5 days.

At 230 included patients a planned interrim analysis will be conducted by an appointed data safety monitoring board of certified healthcare professionals to assess the further continuation of the trial. If favorable assessment, the trial will commence to Stage B.

Patients included in Stage B will be randomized at admission to either usual standard-of-care treatment for 5 days OR inhaled levofloxacin 240mg twice daily for 5 days.

The trial is open-label, which means that both patients and healthcare professionals will know which treatment arm the patient is receiving.

Inclusion criteria

• Hospital admission within 24 hours.
• Clinical suspicion of community-acquired pneumonia necessitating antibiotic treatment.

Defined as one or more of the following:

• Chest X-ray, CT or ultrasound findings consistent with bacterial pneumonia*
• Symptoms consistent with bacterial pneumonia (such as dyspnea, tachypnea, cough or purulent sputum)
• C-reactive protein >50 mg/L OR central body temperature >38.0 °C OR blood leukocytes ≥10.0×109/L (1-3 of these fulfilled).
• Age ≥ 18 years.
• Able to give informed consent.

Exclusion criteria

• Suspected septic shock defined as MAP < 65 mmHg on sequential measurements despite adequate volume resuscitation.
• Oxygen requirement >4L/min to maintain acceptable peripheral oxygen saturation*.
• Significant suspicion of an infection with a focus other than the lungs
• Contraindications for fluoroquinolone treatment, including but not limited to:

• Known allergy to fluoroquinolones or a serious adverse reaction when previously treated with a fluoroquinolone.
• Medical history of myasthenia gravis.
• Reduced kidney function (eGFR < 20 mL/min/1.73 m²).
• Suspected aspiration pneumonia, pulmonary abscess, or pleural empyema / complicated parapneumonic effusion.
• Suspicion of clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) > 480ms).
• Pregnancy**.