Ceftolozane/Tazobactam Continuous Infusion for Infective Exacerbations of Cystic Fibrosis and Bronchiectasis

NCT ID: NCT06035055

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-31
• Study Completion Date: 2024-01-31

Brief 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. 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.

Conditions

Bronchiectasis; Cystic Fibrosis; Pseudomonas Aeruginosa; Burkholderia Cepacia Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ceftolozane/tazobactam 9g infusion

9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days

Group Type: EXPERIMENTAL

Ceftolozane/tazobactam

Intervention Type: DRUG

9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days

Interventions

Ceftolozane/tazobactam

9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Prince Charles Hospital

OTHER_GOV

Sponsor Role: collaborator

Mater

OTHER

Sponsor Role: collaborator

Sunshine Coast Hospital and Health Service

OTHER

Sponsor Role: lead

Responsible Party

Julia Bashford

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julia J Bashford, BSc, MBBS

Role: PRINCIPAL_INVESTIGATOR

Sunshine Coast University Hospital

Andrew Burke, MBBS

Role: PRINCIPAL_INVESTIGATOR

The Prince Charles Hospital

Central Contacts

Julia J Bashford, MBBS FRACP

Role: CONTACT

julia.bashford@health.qld.gov.au

+61752021071

Andrew Burke, MBBS FRACP

Role: CONTACT

Andrew.Burke@health.qld.gov.au

Other Identifiers

CT-2023-CTN-00033-1-v1

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1295-4030

Identifier Type: -

Identifier Source: org_study_id