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

Cystic Fibrosis Clinical Trial

— AZTEC-CF  

Official title:

Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis. An Randomised, Crossover Pilot Study of AZLI Plus Intravenous Colistin® Versus Standard Dual Intravenous Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02894684
• Other study ID #: 2016AZLIND001
• Status: Completed
• Phase: Phase 4
• Start date: January 2017
• Est. completion date: September 2019

Study information

• Verified date: October 2019
• Source: Liverpool Heart and Chest Hospital NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 65 Years

Eligibility

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

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®

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Infection
• Pseudomonas

Intervention

Drug:
• Aztreonam
14 days of AZLI: 75mg TDS PLUS IV Colistin
• Standard Care
14 days of IV Colistin plus one of Tazocin/Ceftazidime/Meropenem/Aztreonam/Fosfomycin

Locations

Country	Name	City	State
United Kingdom	Liverpool Heart & Chest Hospital NHS Trust	Liverpool

Sponsors (2)

Lead Sponsor	Collaborator
Liverpool Heart and Chest Hospital NHS Foundation Trust	University of Liverpool

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average actual change in percent predicted forced expiratory volume at 1 second (FEV1) from Day 1 to Day 14	The actual change in FEV1 (%predicted) from Day 1 of admission to Day 7 & Day 14	14 days
Secondary	Time to first pulmonary exacerbation	Time from discharge to next pulmonary exacerbation	12 months
Secondary	Average change from baseline in the Cystic Fibrosis Quality of Life Questionnaire (CFQ-R)	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	14 days
Secondary	Microbiome changes	Changes in the structure and composition of the microbiome at the beginning and end of each treatment arm	14 days
Secondary	PA sputum counts	Changes in sputum PA counts from the beginning to end of each treatment arm.	14 days
Secondary	Antimicrobial resistance	Prevalence of resistance to antibiotics at the beginning and end of each treatment arm.	14 days