NCT03341741

Combined Dry Powder Tobramycin and Nebulized Colistin Inhalation in CF Patients

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: University Hospital Tuebingen · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

To assess whether the inhalative combination of Tobramycin/Colistin is more effective in reducing Pseudomonas colony forming units (CFUs) and improvement of lung function than Colistin in mono-therapy.

Detailed description

Cystic fibrosis (CF), the most common autosomal recessive disorder in Western countries, is caused by mutations of the cystic fibrosis transmembrane conductance regulator molecule (CFTR) and affects approximately 40.000 patients in Europe. The majority of CF patients develop chronic pulmonary infections with Pseudomonas aeruginosa. These are normally treated with single antibiotics, administered orally, intravenously or inhalatively. Once the infection becomes chronic, eradication of the pathogen is not any more possible due to biofilm formation of the pathogen and increasing resistance. However, inhalative antibiotic combination therapy might be more efficient than single antibiotic therapy in chronically infected CF patients. This notion is supported by previous in vitro and animal studies using Tobramycin/Colistin combination therapy. Importantly, a pilot study in five CF patients who inhaled consecutively Colistin and Tobramycin solutions for 4 week, revealed a decrease of log10 2.52 ± 2.5 cfu of P. aeruginosa in sputum specimens during the course of the treatment compared to baseline values (p=0.027). The treatment was shown to be safe and well tolerated. However, forced expiratory volume in 1 sec (FEV1) did not differ significantly. Taking advantage of the new development of dry powder inhalation (DPI) antibiotics, specifically TOBI© Podhaler, a larger randomised trial has been performed in which the combined TOBI© Podhaler and Colistin treatment is compared to the monotherapy with Colistin.

Conditions

• Cystic Fibrosis With Pulmonary Manifestations

Interventions

Type	Name	Description
DRUG	Tobramycin Powder	TOBI®Podhaler 2 x 112 mg daily for 2 x 28 days (on/off);
DRUG	Colistin	Colistin solution 2 x daily 1 Mega continuously

Timeline

• Start date: 2014-03-11
• Primary completion: 2015-12-19
• Completion: 2016-11-25
• First posted: 2017-11-14
• Last updated: 2017-11-14