BronchiectasisPhase 4CERTAINNCT06035055
Ceftolozane/Tazobactam Continuous Infusion for Infective Exacerbations of Cystic Fibrosis and Bronchiectasis
A Phase 4 study testing Ceftolozane/tazobactam in people with Bronchiectasis and Cystic Fibrosis, run by Sunshine Coast Hospital and Health Service.
Trial summary
The goal of this clinical trial is to assess the feasibility of ceftolozane/tazobactam (C/T) administered on an outpatient parenteral antibiotic therapy programme to patients with a current infective exacerbation of bronchiectasis or cystic fibrosis related to pseudomonas aeruginosa or burkholderia cepacia spp. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bronchiectasis, Cystic Fibrosis, Pseudomonas Aeruginosa
- What is being tested?
- Ceftolozane/tazobactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Oct 2023to Jan 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of CF or non-CF bronchiectasis
- Colonised with P. aeruginosa or BCC species
- Current infectious exacerbation requiring treatment with intravenous antibiotics
- Productive of sputum
Who cannot join
- Unable to consent
- Active pregnancy (as confirmed by urine beta-HCG)
- Not appropriate for OPAT (as determined by treating clinician)
- Estimated Creatinine Clearance < 50 millilitres/min
- History of hypersensitivity reaction to piperacillin/tazobactam or members of the cephalosporin class of antibiotics
- Unable to expectorate
Trial locations and contacts
No sites are listed yet.
Andrew Burke, MBBS FRACP contact
About this study
Official title: The Feasibility of Ceftolozane/Tazobactam Continuous Infusion for Exacerbations of Cystic Fibrosis and Bronchiectasis Treated in an Outpatient Parenteral Antibiotic Therapy (OPAT) Setting
The goal of this clinical trial is to assess the feasibility of ceftolozane/tazobactam (C/T) administered on an outpatient parenteral antibiotic therapy programme to patients with a current infective exacerbation of bronchiectasis or cystic fibrosis related to pseudomonas aeruginosa or burkholderia cepacia spp. organisms. The main question[s] it aims to answer are:
- Is C/T effective, safe, well-tolerated and able to induce clinical and microbiologic response?
- What are mechanisms of antimicrobial resistance are induced by administration of C/T?
Read the detailed description
For patients with cystic fibrosis (CF) and non-CF bronchiectasis, chronic airway infection with Gram-negative organisms such as Pseudomonas aeruginosa and Burkholderia cepacia complex species (BCC) is highly challenging to treat and associated with significant morbidity and mortality. These organisms are naturally resistant towards many antibiotic classes, limiting the available arsenal of effective antibiotics for their treatment and eradication. Therefore, there is a pressing need for new antimicrobial therapy options for infective exacerbations associated with these organisms.
There are clear logistical and financial benefits for acute infective exacerbations of CF and non-CF bronchiectasis to be managed on OPAT programs. Many acute infective exacerbations can be safely managed in this way, and a substantial body of evidence supports non-inferiority of OPAT compared with inpatient care. From a logistical perspective, feasibility of OPAT programs is greatly improved by antibiotics being infused over a 24-hour period rather than via bolus several times per day. Unfortunately, many mainstay anti-pseudomonal and anti-Burkholderia antibiotics (including meropenem, imipenem and ceftazidime) are not stable for 24 hours at room/body temperature therefore are unsuitable for use on OPAT.
This study aims to assess viability of ceftolozane/tazobactam (C/T) administered via OPAT in adult patients with exacerbations of CF or non-CF bronchiectasis. Secondary aims are to describe clinical outcomes of patients receiving C/T, tolerability of C/T, relative sputum bacterial load throughout treatment and assess development of resistance to C/T and other antibiotics. We aim to recruit 30 patients, colonized with either pseudomonas aeruginosa or burkholderia cepacia complex, with a current infectious exacerbation requiring intravenous antibiotic treatment. We propose to administer C/T via infusion for 10-14 days with review at day 0-3, 5-7 and 10-14. Blood testing, sputum testing, lung function testing, administration of CF- and bronchiectasis-specific questionnaires and adverse event reporting will be carried out at these times. Serum levels of C/T will be monitored using a validated assay. Clinical review at day 28-42 will be carried out to assess for recrudescence of symptoms and further need for antibiotics and a follow-up phone call will be made at 3 months to assess whether any further antibiotics were needed for new/recrudescent symptoms of infection.
We expect to find that C/T is safe, well-tolerated and effective in treating infective exacerbations of bronchiectasis in OPAT settings. We expect to find that bacterial density in sputum samples reduces over the course of treatment, and that development of antimicrobial resistance is minimal.
- Being tested
- Ceftolozane/tazobactam
- Medical subject headings
- Bronchiectasis, Cystic Fibrosis, Pseudomonas Infections, Burkholderia Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftolozane/tazobactamDrug
9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days
| Study group | Role | What they receive |
|---|---|---|
| Ceftolozane/tazobactam 9g infusion | Experimental | 9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days Receives: Drug: Ceftolozane/tazobactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis.
The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis will be assessed. Feasibility will be determined as a composite of clinical response (as assessed by disease-specific questionnaires, serum inflammatory marker monitoring and spirometry in the case of patients with cystic fibrosis), adverse events and report of relapse of respiratory infection at 3 months.
Measured: Day 0 to day 90 post commencement of intervention.
Secondary outcomes (3)
Safety and tolerability
Safety and tolerability of continuous infusion ceftolozane/tazobactam. Ceftolozane/tazobactam has a very similar adverse event (AE) profile to other broad spectrum intravenous antibiotics, e.g. piperacillin/tazobactam and meropenem. Possible symptomatic AE's include: nausea, diarrhoea, headache, vomiting, constipation, insomnia, rash and fever. These will be assessed direct questioning of participants at the time of research visits, by clinical examination and and by participants self-reporting symptoms of concern to the research team any time during or after their course of ceftolozane/tazobactam. Possible laboratory abnormalities include: liver function test derangement and acute kidney injury. These will be monitored by regular blood tests during and after the course of ceftolozane/tazobactam.
Measured: Day 0 to day 90 post commencement of intervention.
Relative bacterial load
To describe relative bacterial load over the course of ceftolozane/tazobactam treatment as assessed by quantitative PCR (qPCR) on sputa.
Measured: Day 0-1, Day 5-7, Day 10-14, Day 28-42
In vitro antimicrobial susceptibility/resistance
To describe in vitro antimicrobial susceptibility of airway pathogens to ceftolozane/tazobactam and other anti-pseudomonal/anti-Burkholderia antibiotics over the course of ceftolozane/tazobactam treatment. This will be determined by a composite outcome of antimicrobial susceptibility testing, whole-genome sequencing (WGS), culturomic sequencing, and bioinformatic analysis.
Measured: Day 0-1, Day 5-7, Day 10-14, Day 28-42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study startOct 2023 (estimated)
- Primary completionOct 2023 (estimated)
- Study completionJan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BronchiectasisStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- 30 patients will be recruited and will receive the study intervention.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunshine Coast Hospital and Health Service
- Sponsor type
- University, hospital or other
- Collaborators
- The Prince Charles Hospital, Mater
- Responsible party
- Principal investigator, Julia Bashford, Sunshine Coast Hospital and Health Service
- Investigators
- Julia J Bashford, BSc, MBBS, Principal investigator, Sunshine Coast University HospitalAndrew Burke, MBBS, Principal investigator, The Prince Charles Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06035055
- Sponsor's protocol ID
- U1111-1295-4030
- Other IDs
- CT-2023-CTN-00033-1-v1
- Acronym
- CERTAIN
- Status last verified
- Sep 2023
- First submitted
- 6 Sep 2023
- Last updated
- 13 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Only de-identified, line-by-line data will be be provided to researchers who provide a sound proposal to allow for meta-analyses requiring individual participant data (IPD). Data will be available immediately following publication, with there being no pre-determined end date on IPD sharing.
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Feasibility of Ceftolozane/Tazobactam Continuous Infusion for Exacerbations of Cystic Fibrosis and Bronchiectasis Treated in an Outpatient Parenteral Antibiotic Therapy (OPAT) Setting
- ClinicalTrials.gov ID
- NCT06035055
- Acronym / sponsor ID
- CERTAIN / U1111-1295-4030
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Sunshine Coast Hospital and Health ServiceUniversity, hospital or other
- Collaborators
- The Prince Charles Hospital, Mater
- Study start
- Oct 2023 (estimated)
- Primary completion
- Oct 2023 (estimated)
- Study completion
- Jan 2024 (estimated)
- First posted
- 13 Sep 2023 (actual)
- 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.
The goal of this clinical trial is to assess the feasibility of ceftolozane/tazobactam (C/T) administered on an outpatient parenteral antibiotic therapy programme to patients with a current infective exacerbation of bronchiectasis or cystic fibrosis related to pseudomonas aeruginosa or burkholderia cepacia spp. organisms. The main question[s] it aims to answer are:
- Is C/T effective, safe, well-tolerated and able to induce clinical and microbiologic response?
- What are mechanisms of antimicrobial resistance are induced by administration of C/T?
Detailed description
For patients with cystic fibrosis (CF) and non-CF bronchiectasis, chronic airway infection with Gram-negative organisms such as Pseudomonas aeruginosa and Burkholderia cepacia complex species (BCC) is highly challenging to treat and associated with significant morbidity and mortality. These organisms are naturally resistant towards many antibiotic classes, limiting the available arsenal of effective antibiotics for their treatment and eradication. Therefore, there is a pressing need for new antimicrobial therapy options for infective exacerbations associated with these organisms.
There are clear logistical and financial benefits for acute infective exacerbations of CF and non-CF bronchiectasis to be managed on OPAT programs. Many acute infective exacerbations can be safely managed in this way, and a substantial body of evidence supports non-inferiority of OPAT compared with inpatient care. From a logistical perspective, feasibility of OPAT programs is greatly improved by antibiotics being infused over a 24-hour period rather than via bolus several times per day. Unfortunately, many mainstay anti-pseudomonal and anti-Burkholderia antibiotics (including meropenem, imipenem and ceftazidime) are not stable for 24 hours at room/body temperature therefore are unsuitable for use on OPAT.
This study aims to assess viability of ceftolozane/tazobactam (C/T) administered via OPAT in adult patients with exacerbations of CF or non-CF bronchiectasis. Secondary aims are to describe clinical outcomes of patients receiving C/T, tolerability of C/T, relative sputum bacterial load throughout treatment and assess development of resistance to C/T and other antibiotics. We aim to recruit 30 patients, colonized with either pseudomonas aeruginosa or burkholderia cepacia complex, with a current infectious exacerbation requiring intravenous antibiotic treatment. We propose to administer C/T via infusion for 10-14 days with review at day 0-3, 5-7 and 10-14. Blood testing, sputum testing, lung function testing, administration of CF- and bronchiectasis-specific questionnaires and adverse event reporting will be carried out at these times. Serum levels of C/T will be monitored using a validated assay. Clinical review at day 28-42 will be carried out to assess for recrudescence of symptoms and further need for antibiotics and a follow-up phone call will be made at 3 months to assess whether any further antibiotics were needed for new/recrudescent symptoms of infection.
We expect to find that C/T is safe, well-tolerated and effective in treating infective exacerbations of bronchiectasis in OPAT settings. We expect to find that bacterial density in sputum samples reduces over the course of treatment, and that development of antimicrobial resistance is minimal.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 30 patients will be recruited and will receive the study intervention.
| Arm | Type | Receives |
|---|---|---|
| Ceftolozane/tazobactam 9g infusion | Experimental | Drug: Ceftolozane/tazobactam9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of CF or non-CF bronchiectasis
- Colonised with P. aeruginosa or BCC species
- Current infectious exacerbation requiring treatment with intravenous antibiotics
- Productive of sputum
Key exclusion criteria (6 listed)
- Unable to consent
- Active pregnancy (as confirmed by urine beta-HCG)
- Not appropriate for OPAT (as determined by treating clinician)
- Estimated Creatinine Clearance < 50 millilitres/min
- History of hypersensitivity reaction to piperacillin/tazobactam or members of the cephalosporin class of antibiotics
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 |
|---|---|---|
| Ceftolozane/tazobactam9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days | Drug | Ceftolozane/tazobactam 9g infusion |
Primary outcome
The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis.
Time frame: Day 0 to day 90 post commencement of intervention.
The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis will be assessed. Feasibility will be determined as a composite of clinical response (as assessed by disease-specific questionnaires, serum inflammatory marker monitoring and spirometry in the case of patients with cystic fibrosis), adverse events and report of relapse of respiratory infection at 3 months.
3 secondary outcomes
Safety and tolerability
Time frame: Day 0 to day 90 post commencement of intervention.
Relative bacterial load
Time frame: Day 0-1, Day 5-7, Day 10-14, Day 28-42
In vitro antimicrobial susceptibility/resistance
Time frame: Day 0-1, Day 5-7, Day 10-14, Day 28-42
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Individual participant dataSharing planned: Yes. Only de-identified, line-by-line data will be be provided to researchers who provide a sound proposal to allow for meta-analyses requiring individual participant data (IPD). Data will be available immediately following publication, with there being no pre-determined end date on IPD sharing.
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Bronchiectasis
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.
Andrew Burke, MBBS FRACP contact
Julia J Bashford, BSc, MBBS principal investigator
Sunshine Coast University Hospital
Andrew Burke, MBBS principal investigator
The Prince Charles Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ceftolozane/tazobactam in people with Bronchiectasis and Cystic Fibrosis, run by Sunshine Coast Hospital and Health Service.
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 4 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: status not confirmed, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Julia J Bashford, MBBS FRACP (+61752021071, julia.bashford@health.qld.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis. (time frame: Day 0 to day 90 post commencement of intervention.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Sep 2023.