Cystic FibrosisPhase 4AZTEC-CFNCT02894684
Aztreonam for Inhalation Solution (AZLI) for the Treatment of Exacerbations of Cystic Fibrosis
A Phase 4 study testing Aztreonam in people with Cystic Fibrosis and Infection, run by Liverpool Heart and Chest Hospital NHS Foundation Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 16 to 65 years, men only
- Conditions the study is for
- Cystic Fibrosis, Infection, Pseudomonas
- What is being tested?
- Aztreonam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2017to Sep 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of CF
- Patients aged 18 - 65 years of age who can give informed consent
- FEV1 >25% or <75% predicted (in keeping with Cayston® license)
- Admitted to the Liverpool Heart \& Chest Hospital with an exacerbation of CF pulmonary disease
- Presence of PA in lower respiratory tract cultures in the 6 months prior
Who cannot join
- Documented allergy to beta-lactam antibiotics or IV Colistin
- Growth of Burkholderia Cepacia Complex (BCC) within 2 years
- Pregnancy
- Previous organ transplant
- Receiving other clinical trial medication
- Already prescribed regular Cayston®
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Liverpool Heart & Chest Hospital NHS Trust
Liverpool, L3 9BZ
About this study
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
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.
Read the 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.
- Conditions
- Cystic Fibrosis, Infection, Pseudomonas
- Being tested
- Aztreonam, Standard Care
- Medical subject headings
- Cystic Fibrosis, Infections, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AztreonamDrug
Also called Cayston, AZLI
14 days of AZLI: 75mg TDS PLUS IV Colistin
Standard CareDrug
14 days of IV Colistin plus one of Tazocin/Ceftazidime/Meropenem/Aztreonam/Fosfomycin
| Study group | Role | What they receive |
|---|---|---|
| AZLI then Standard Care | Experimental | Upon first exacerbation this arm will receive AZLI, on their second they will receive standard care Receives: Drug: Aztreonam; Drug: Standard Care |
| Standard Care then AZLI | Active comparator | Upon first exacerbation this arm will receive standard care, on the second exacerbation this arm will receive AZLI Receives: Drug: Aztreonam; Drug: Standard Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 days
Secondary outcomes (5)
Time to first pulmonary exacerbation
Time from discharge to next pulmonary exacerbation
Measured: 12 months
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
Measured: 14 days
Microbiome changes
Changes in the structure and composition of the microbiome at the beginning and end of each treatment arm
Measured: 14 days
PA sputum counts
Changes in sputum PA counts from the beginning to end of each treatment arm.
Measured: 14 days
Antimicrobial resistance
Prevalence of resistance to antibiotics at the beginning and end of each treatment arm.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2016 (estimated)
- Study startJan 2017
- Primary completionFeb 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liverpool Heart and Chest Hospital NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liverpool
- Responsible party
- Sponsor
- Investigators
- Freddy Frost, BMBS BMedSci, Principal investigator, Liverpool Heart & Chest Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02894684
- Sponsor's protocol ID
- 2016AZLIND001
- Acronym
- AZTEC-CF
- Status last verified
- Oct 2019
- First submitted
- 1 Sep 2016
- Last updated
- 7 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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. 2021 Nov;20(6):994-1002. doi: 10.1016/j.jcf.2020.12.012. Epub 2021 Jan 7.
PubMed 33358119
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02894684
- Acronym / sponsor ID
- AZTEC-CF / 2016AZLIND001
- Conditions
- Cystic Fibrosis, Infection, Pseudomonas
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Liverpool Heart and Chest Hospital NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Liverpool
- Study start
- Jan 2017 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 9 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZLI then Standard Care | Experimental | Drug: Aztreonam, Drug: Standard CareUpon first exacerbation this arm will receive AZLI, on their second they will receive standard care |
| Standard Care then AZLI | Active comparator | Drug: Aztreonam, Drug: Standard CareUpon first exacerbation this arm will receive standard care, on the second exacerbation this arm will receive AZLI |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed diagnosis of CF
- Patients aged 18 - 65 years of age who can give informed consent
- FEV1 >25% or <75% predicted (in keeping with Cayston® license)
- Admitted to the Liverpool Heart \& Chest Hospital with an exacerbation of CF pulmonary disease
- Presence of PA in lower respiratory tract cultures in the 6 months prior
Key exclusion criteria (6 listed)
- Documented allergy to beta-lactam antibiotics or IV Colistin
- Growth of Burkholderia Cepacia Complex (BCC) within 2 years
- Pregnancy
- Previous organ transplant
- Receiving other clinical trial medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AztreonamAlso: Cayston, AZLI14 days of AZLI: 75mg TDS PLUS IV Colistin | Drug | AZLI then Standard Care, Standard Care then AZLI |
| Standard Care14 days of IV Colistin plus one of Tazocin/Ceftazidime/Meropenem/Aztreonam/Fosfomycin | Drug | AZLI then Standard Care, Standard Care then AZLI |
Primary outcome
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
5 secondary outcomes
Time to first pulmonary exacerbation
Time frame: 12 months
Average change from baseline in the Cystic Fibrosis Quality of Life Questionnaire (CFQ-R)
Time frame: 14 days
Microbiome changes
Time frame: 14 days
PA sputum counts
Time frame: 14 days
Antimicrobial resistance
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2019.
- Derived from this study: PubMed 33358119Frost 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. 2021 Nov;20(6):994-1002. doi: 10.1016/j.jcf.2020.12.012. Epub 2021 Jan 7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Freddy Frost, BMBS BMedSci principal investigator
Liverpool Heart & Chest Hospital NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aztreonam in people with Cystic Fibrosis and Infection, run by Liverpool Heart and Chest Hospital NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average actual change in percent predicted forced expiratory volume at 1 second (FEV1) from Day 1 to Day 14 (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02894684, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2019.