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

• ClinicalTrials.gov Identifier: NCT02894684
• Recruitment Status: Completed
• First Posted: September 9, 2016
• Last Update Posted: October 7, 2019
• Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust
• Collaborator: University of Liverpool
• Information provided by (Responsible Party): Liverpool Heart and Chest Hospital NHS Foundation Trust

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis; Infection; Pseudomonas	Drug: Aztreonam; Drug: Standard Care	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 2017
• Actual Primary Completion Date: February 2019
• Actual Study Completion Date: September 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: AZLI then Standard Care; Upon first exacerbation this arm will receive AZLI, on their second they will receive standard care	Drug: Aztreonam; 14 days of AZLI: 75mg TDS PLUS IV Colistin; Other Names: Cayston; AZLI; Drug: Standard Care; 14 days of IV Colistin plus one of Tazocin/Ceftazidime/Meropenem/Aztreonam/Fosfomycin
Active Comparator: Standard Care then AZLI; Upon first exacerbation this arm will receive standard care, on the second exacerbation this arm will receive AZLI	Drug: Aztreonam; 14 days of AZLI: 75mg TDS PLUS IV Colistin; Other Names: Cayston; AZLI; Drug: Standard Care; 14 days of IV Colistin plus one of Tazocin/Ceftazidime/Meropenem/Aztreonam/Fosfomycin

Outcome Measures

Primary Outcome Measures :

1. Average actual change in percent predicted forced expiratory volume at 1 second (FEV1) from Day 1 to Day 14 [ Time Frame: 14 days ]
   The actual change in FEV1 (%predicted) from Day 1 of admission to Day 7 & Day 14

Secondary Outcome Measures :

1. Time to first pulmonary exacerbation [ Time Frame: 12 months ]
   Time from discharge to next pulmonary exacerbation
2. Average change from baseline in the Cystic Fibrosis Quality of Life Questionnaire (CFQ-R) [ Time Frame: 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
3. Microbiome changes [ Time Frame: 14 days ]
   Changes in the structure and composition of the microbiome at the beginning and end of each treatment arm
4. PA sputum counts [ Time Frame: 14 days ]
   Changes in sputum PA counts from the beginning to end of each treatment arm.
5. Antimicrobial resistance [ Time Frame: 14 days ]
   Prevalence of resistance to antibiotics at the beginning and end of each treatment arm.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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®

Contacts and Locations

Locations

United Kingdom

Liverpool Heart & Chest Hospital NHS Trust

Liverpool, United Kingdom, L3 9BZ

Sponsors and Collaborators

Liverpool Heart and Chest Hospital NHS Foundation Trust

University of Liverpool

Investigators

• Principal Investigator: Freddy Frost, BMBS BMedSci; Liverpool Heart & Chest Hospital NHS Foundation Trust

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Frost F, Young GR, Wright L, Miah N, Smith DL, Winstanley C, Walshaw MJ, Fothergill JL, Nazareth D. The clinical and microbiological utility of inhaled aztreonam lysine for the treatment of acute pulmonary exacerbations of cystic fibrosis: An open-label randomised crossover study (AZTEC-CF). J Cyst Fibros. 2020 Dec 21. pii: S1569-1993(20)30944-9. doi: 10.1016/j.jcf.2020.12.012. [Epub ahead of print]

• Responsible Party: Liverpool Heart and Chest Hospital NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT02894684
• Other Study ID Numbers: 2016AZLIND001
• First Posted: September 9, 2016
• Last Update Posted: October 7, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Aztreonam; Anti-Bacterial Agents; Anti-Infective Agents