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

October 3, 2019 updated by: Liverpool Heart and Chest Hospital NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Liverpool, United Kingdom, L3 9BZ
        • Liverpool Heart & Chest Hospital NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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®

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first pulmonary exacerbation
Time Frame: 12 months
Time from discharge to next pulmonary exacerbation
12 months
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
14 days
Microbiome changes
Time Frame: 14 days
Changes in the structure and composition of the microbiome at the beginning and end of each treatment arm
14 days
PA sputum counts
Time Frame: 14 days
Changes in sputum PA counts from the beginning to end of each treatment arm.
14 days
Antimicrobial resistance
Time Frame: 14 days
Prevalence of resistance to antibiotics at the beginning and end of each treatment arm.
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liverpool Heart and Chest Hospital NHS Foundation Trust

Collaborators

University of Liverpool

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

September 1, 2019

Study Registration Dates

First Submitted

September 1, 2016

First Submitted That Met QC Criteria

September 8, 2016

First Posted (Estimate)

September 9, 2016

Study Record Updates

Last Update Posted (Actual)

October 7, 2019

Last Update Submitted That Met QC Criteria

October 3, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016AZLIND001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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