None listed
Conditions
Brief summary
BEAT CF is a national, multi-site project which aims to learn and implement , which of the antibiotics commonly used to treat lung infections are best. There is no single standard of care for managing CF pulmonary exacerbations. Standard care comprises a range of interventions and varies across and within CF treatment centres and may evolve over the course of the PEx Treatment Platform. At the time of initiation of the PEx Treatment Platform Protocol, management of pulmonary exacerbations generally involves the use of one or more intravenous (IV) antibiotic therapies. The duration of IV antibiotic therapy is typically 14 days, and generally ranges from 10 days to 21 days. A recent RCT found evidence that 10 days was non-inferior to 14 days of IV antibiotics therapy in those with a rapid treatment response, and found no evidence that 21 days was superior to 14 days of IV antibiotics therapy in those without a rapid treatment response. Most Australian clinicians manage pulmonary exacerbations with an antipseudomonal beta-lactam or carbapenem, combined with a non-beta lactam antibiotic - most typically the aminoglycoside IV tobramycin. Some, but not all, clinicians reserve the use of IV aminoglycoside for patients known to be colonised with Pseudomonas aeruginosa. Some, but not all, clinicians use the results of microbiology and in vitro susceptibilities to guide antibiotic selection. Many centres provide additional antibiotic cover targeted to specific pathogens, but only if identified on sputum microbiology, e.g. for Stenotrophomonas maltophilia or Staphylococcus aureus. CF clinicians prescribe physiotherapy for airway clearance as a core part of the management of CF pulmonary exacerbations, though there is variation in the nature and frequency of this therapy. Some, but not all, CF clinicians all prescribe muco-active or anti-inflammatory therapies. As for the use of antibiotics, there is no evidence to support any of these modes of treatment as a single best standard of care. The primary objectives, outcomes and endpoints for the PEx Cohort were informed by a systematic review of the literature and involvement of key clinical and consumer stakeholders.
Interventions
The intervention is a Prescription for the Assigned antibiotic at the commencement of intensive therapy made by the Responsible Clinician or their authorised delegate.
For each of the 4 treatment options:
The Dose and Duration prescribed is not fixed, and will ultimately be at the discretion of the Responsible Clinician in adherence with local Cystic Fibrosis (CF) centre /hospital guidelines and policies. The protocol requires that the antibiotic has a planned duration of at least 7 days. No ma
The intervention is a Prescription for the Assigned antibiotic at the commencement of intensive therapy made by the Responsible Clinician or their authorised delegate. For each of the 4 treatment options: The Dose and Duration prescribed is not fixed, and will ultimately be at the discretion of the Responsible Clinician in adherence with local Cystic Fibrosis (CF) centre /hospital guidelines and policies. The protocol requires that the antibiotic has a planned duration of at least 7 days. No maximum duration of treatment is specified. Assigned antibiotics include: 1. Intravenous Piperacillin + tazobactam As a guide, administration by intravenous (IV) infusion over 30 minutes or longer, or by continuous infusion over 24 hours. Dose adjustment may be required in cases of impaired renal function (Creatinine Clearance of <40ml/min). 2. Intravenous Cefepime As a guide, IV Cefepime should be given by IV push over several minutes, OR IV infusion over up to 30 minutes, OR continuous IV infusion over 24 minutes. It may also be given by intramuscular (IM) injection. Dose adjustment may be required in cases of impaired renal function (Creatinine Clearance of <50ml/min). 3. Intravenous Ceftazadime As a guide, Administration by IV bolus over several minutes, or as an infusion over up to 30 minutes. Doses <1000mg may also be given by IM injection. Dose adjustment may be required in cases of impaired renal function (Creatinine Clearance of <50ml/min). 4. Intravenous Ceftriaxone As a guide, Administration by IV infusion over 30 minutes, or by push over 5-15 minutes. It may also be given by IM injection. May be required in cases of significant renal impairment (creatinine clearance of <10mL/minute). Adherence to the assigned intervention will be monitored by the detailed information about intensive therapies that is captured in the BEAT CF database. This information will be transcribed from the hospital medical records into the BEAT CF database by dedicated BEAT CF site coordinators at each site. Participants will only be randomised to one of these treatment arms for any single episode of a pulmonary exacerbation. If participants do not respond to the first treatment the clinician is free to decide which therapy the participant shall be switched to. There will be no subsequent randomsiation within a single pulmonary exacerbation episode.
Sponsors
University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be enrolled in the BEAT CF PEx Cohort (ACTRN12621000638831). 2. Documented informed consent to participate in the Backbone antibiotics Domain. 3. Are eligible for at least two Interventions in the Backbone Antibiotic Domain available at the clinical Site. 4. Must be able to reliably perform spirometry.
Exclusion criteria
1. The person is unable to reliably perform spirometry (for example due to young age) 2. The person’s Responsible Clinician deems enrolment in the PEx Backbone Antibiotic Domain is not in their best interest. A participant will be excluded from Assignment to a specific Intervention in the Backbone Antibiotics Domain if: 1. They have a known or suspected significant drug hypersensitivity to that antibiotic 2. They have another recognised contraindication to that antibiotic 3. The Intervention is deemed unacceptable by the Responsible Clinician e.g. because of a poor treatment response to that antibiotic (requiring a change in antibiotic treatment) in the preceding 12 months
Outcome results
None listed