Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis

Phase 4

Completed

• Conditions: Infection; Cystic Fibrosis; Pseudomonas
• Interventions: Drug: Aztreonam; Drug: Standard Care

• Registration Number: NCT02894684
• Lead Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust

Brief Summary

This study evaluates the role of AZLI in the treatment of acute pulmonary exacerbations of CF. For consecutive exacerbations patients will receive AZLI + IV Colistin, or two IV anti-pseudomonals.

Detailed Description

AZLI, marketed as Cayston, is an inhaled beta-lactam antibiotic. It has a license for the chronic suppression of Pseudomonas aeruginosa (PA). Current standard practice dictates the use of two IV antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations. The increasing survival, and hence population, in CF means that newer antimicrobial strategies are required in order to manage antimicrobial resistance, minimise adverse systemic effects of heavy antimicrobial exposure and also make effective use of resources. Inhaled antibiotics are commonly used in the chronic suppression of PA yet their use has not been thoroughly investigated in acute pulmonary exacerbation. Inhaled antibiotics deliver their drugs directly to the target-site with minimal systemic absorbance, making them an attractive candidate for treatment of acute exacerbations.

Recently, it has become apparent that the bacterial community is much more complex than initially thought. The microbiome, a term used to describe the polymicrobial community in the lungs, has become apparent due to the use of modern culture-independent methods to detect bacteria. The microbiome changes in composition and structure around the time of exacerbations and in response to treatment, although these changes have not been prospectively characterised.

We have designed an open-label randomised, controlled cross-over trial to investigate the clinical effectiveness of of AZLI in the treatment of acute pulmonary exacerbation, whilst simultaneously comparing the effect inhaled and intravenous antibiotics have on the microbiome.

Study Timeline

• Study First Submitted: 2016-09-01
• Study First Submitted QC: 2016-09-08
• Study First Posted: 2016-09-09
• Study Start: 2017-01
• Primary Completion: 2019-02
• Study Completion: 2019-09
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-03
• Last Update Posted: 2019-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1. Confirmed diagnosis of CF
2. Patients aged 18 - 65 years of age who can give informed consent
3. FEV1 >25% or <75% predicted (in keeping with Cayston® license)
4. Admitted to the Liverpool Heart & Chest Hospital with an exacerbation of CF pulmonary disease
5. Presence of PA in lower respiratory tract cultures in the 6 months prior

Read More

Exclusion Criteria

1. Documented allergy to beta-lactam antibiotics or IV Colistin
2. Growth of Burkholderia Cepacia Complex (BCC) within 2 years
3. Pregnancy
4. Previous organ transplant
5. Receiving other clinical trial medication
6. Already prescribed regular Cayston®

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AZLI then Standard Care	Aztreonam	Upon first exacerbation this arm will receive AZLI, on their second they will receive standard care
Standard Care then AZLI	Standard Care	Upon first exacerbation this arm will receive standard care, on the second exacerbation this arm will receive AZLI
AZLI then Standard Care	Standard Care	Upon first exacerbation this arm will receive AZLI, on their second they will receive standard care
Standard Care then AZLI	Aztreonam	Upon first exacerbation this arm will receive standard care, on the second exacerbation this arm will receive AZLI

Primary Outcome Measures

Name	Time	Method
Average actual change in percent predicted forced expiratory volume at 1 second (FEV1) from Day 1 to Day 14	14 days	The actual change in FEV1 (%predicted) from Day 1 of admission to Day 7 \& Day 14

Secondary Outcome Measures

Name	Time	Method
Average change from baseline in the Cystic Fibrosis Quality of Life Questionnaire (CFQ-R)	14 days	Average change from baseline (Day 1) in the CFQ-R Respiratory Symptom Score (RSS) at the end (Day 14) of each arm of the study
Microbiome changes	14 days	Changes in the structure and composition of the microbiome at the beginning and end of each treatment arm
Antimicrobial resistance	14 days	Prevalence of resistance to antibiotics at the beginning and end of each treatment arm.
Time to first pulmonary exacerbation	12 months	Time from discharge to next pulmonary exacerbation
PA sputum counts	14 days	Changes in sputum PA counts from the beginning to end of each treatment arm.

Trial Locations

Locations (1)

Liverpool Heart & Chest Hospital NHS Trust; 🇬🇧 Liverpool, United Kingdom