Randomized double‑blind trial of inhaled colistimethate sodium vs oral ciprofloxacin vs placebo for Pseudomonas aeruginosa eradication in adults with bronchiectasis

The primary objective is to determine the efficacy of three distinct antibiotic regimens compared with placebo for achieving microbiological eradication of Pseudomonas aeruginosa in adults with non‑cystic fibrosis bronchiectasis who present with a primary infection; eradication is defined by a negative sputum culture obtained three months after initiation of therapy, reflecting a clinically relevant endpoint aimed at reducing chronic colonisation, exacerbation risk, and disease progression.

Adults older than 18 years of both sexes were enrolled; the sponsor did not provide the total number of participants. Eligible individuals had a diagnosis of bronchiectasis confirmed by clinical symptoms and high‑resolution computed tomography within the preceding five years and a primary infection with Pseudomonas aeruginosa meeting defined culture criteria. Participants were required to be clinically stable, with no exacerbations in the month before screening, no need for intravenous therapy or hospitalization, and to sign informed consent. No specific lifestyle restrictions regarding diet, physical activity, or other habits were stipulated.

The PRIME trial is a randomized, double-blind, parallel‑group study comparing three antibiotic regimens with placebo for eradication of primary Pseudomonas aeruginosa infection in adults with bronchiectasis. After an eligibility screening visit, participants who meet inclusion criteria are randomized 1:1:1:1 to receive inhaled colistimethate sodium, oral ciprofloxacin (250 mg or 500 mg), or matching placebo (0.9 % sodium chloride infusion or inert cellulose formulation). The treatment phase lasts four weeks, followed by scheduled assessments at 1, 2, and 3 months to determine the primary endpoint of microbiological eradication (negative sputum or bronchoscopic cultures at month 3). Additional visits at 6 and 12 months evaluate sustained eradication, exacerbation frequency, safety, quality of life, biomarkers and cost outcomes. The total participant involvement is approximately 12 months, concluding with an end‑of‑study visit at month 12. Early termination may occur due to serious adverse events, protocol non‑compliance, withdrawal of consent, or inability to complete required assessments.

The investigational inhalation therapy consists of colistimethate sodium supplied as a powder for solution for nebulisation (Colfinair). The product is provided as a nebuliser solution for inhalation, delivering a dose of 4 million IU per administration. Dosing follows the study schedule and is performed using a standard jet nebuliser; each dose is administered according to the prescribed frequency.

The oral investigational regimen comprises ciprofloxacin film‑coated tablets (Normon) of 250 mg and 500 mg strength. Both tablets are taken to achieve a total daily dose of 750 mg, administered orally in divided doses as defined by the protocol. Tablet ingestion is scheduled at consistent times each day to maintain therapeutic plasma concentrations.

The inhalation control arm utilizes a 0.9 % sodium chloride solution for infusion, presented as a solution for inhalation and administered at a dose of 4 million IU per inhalation. This placebo matches the active nebuliser solution in appearance and volume and follows the same dosing schedule as the active inhaled product.

An oral control formulation consists of microcrystalline cellulose combined with colloidal silica, formulated to resemble the ciprofloxacin tablets. This oral placebo is administered with the same frequency and timing as the active ciprofloxacin tablets.

Compliance monitoring includes recording of each administered dose in a case report form, pill count reconciliation at each visit, and verification of nebuliser usage through device logs or patient diaries. Drug accountability procedures are applied to ensure adherence to the assigned regimen.

Efficacy will be evaluated primarily by microbiological eradication of Pseudomonas aeruginosa, defined as a negative culture obtained from sputum or, when performed as part of routine care, from a bronchoscopic sample at 3 months after the start of treatment.

Secondary efficacy assessments will include early eradication measured by negative cultures at 1 month and 2 months, and sustained eradication assessed at 6 months and 12 months. Additional secondary parameters are the frequency of disease exacerbations, quality‑of‑life scores, serum biomarker concentrations, and health‑care costs. All microbiological samples will be processed using standard laboratory culture techniques. Exacerbation frequency will be recorded through patient diaries and clinical visits. Quality‑of‑life will be captured with validated questionnaires, and serum biomarkers will be quantified by approved laboratory assays at the specified time points.