NCT03093974

Efficacy and Safety of Inhaled CMS in Bronchiectasis Subjects With Chronic P. Aeruginosa Infection. (PROMIS-I)

Double-blind, Placebo-controlled, Clinical Trial on Efficacy and Safety of 12-months Therapy With Inhaled Colistimethate Sodium in the Treatment of Subjects With Non-cystic Fibrosis Bronchiectasis Chronically Infected With P. Aeruginosa

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 377 (actual)
• Sponsor: Zambon SpA · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The objective of the trial was to investigate the effect of the use of inhaled CMS, administered b.i.d. via a specific nebuliser for 12 months, compared to placebo in subjects with NCFB chronically infected with P. aeruginosa on the annualised frequency of pulmonary exacerbations.

Detailed description

This was a randomised, multi-centre, double-blind, placebo-controlled, parallel group interventional trial in subjects with NCFB and chronic P. aeruginosa infection. Subjects were randomised to CMS or placebo in a 1:1 ratio. The study consisted of seven clinic visits over one year with a follow-up phone call two weeks after discontinuation of treatment. Additional clinic visits, where feasible,and weekly phone calls were conducted during or after pulmonary exacerbations (or any episodes of pneumonia) until resolution. All planned and unscheduled visits were preferably performed at sites, whenever possible. If on site visits after Visit 2 could not be performed at site due to COVID-19, remote visits (e.g., by telephone) were permitted. Mandatory on site visits were kept for Screening Visit (Visit 1) and Randomisation (Visit 2). If the final visit (Visit 7) had to be conducted remotely, then subjects were asked to return to the clinic for on-site assessments at the earliest opportunity.

Conditions

• Non Cystic Fibrosis Bronchiectasis

Interventions

Type	Name	Description
DRUG	CMS	1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d dosing). The 1 MIU/mL CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (\~10 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d (morning and evening) over a period of 12 months. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g., salbutamol /albuterol), supplied by the Sponsor, could be taken to improve tolerability.
OTHER	Placebo	1 ml saline solution 0.45%. the placebo was made up of identical empty glass vials to which the same saline diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to maintain the blind.

Timeline

• Start date: 2017-06-06
• Primary completion: 2021-04-09
• Completion: 2021-04-09
• First posted: 2017-03-28
• Last updated: 2023-11-15
• Results posted: 2023-11-15

Locations

85 sites across 12 countries: Australia, Belgium, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Portugal, Spain, Switzerland, United Kingdom