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. Most Australian clinicians manage pulmonary exacerbations with an antipseudomonal beta-lactam or carbapenem, combined with a non-beta lactam antibiotic - most typically the aminoglycoside tobramycin given intravenously (IV). Tobramycin can also be given via inhalation. Inhaled tobramycin is widely used for outpatient management, it is rarely used as part of inpatient management of PEx. This particular domain to the BEAT CF PEx treatment platform aims to find out if there is any gain in providing tobramycin in addition to ‘backbone’ antibiotic therapy. Also, it will assess there is any difference in giving tobramycin by the IV or inhaled route, and whether no tobramycin is non-inferior to the IV or inhaled tobramycin. Some 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. 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 in those without a rapid treatment response. 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 (or no Adjunct Antibiotic) at the commencement of intensive therapy made by the Responsible Clinician or their authorised delegate.
For each of the 2 treatment options involving adjunct antibiotics:
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 ant
The intervention is a Prescription for the Assigned antibiotic (or no Adjunct Antibiotic) at the commencement of intensive therapy made by the Responsible Clinician or their authorised delegate. For each of the 2 treatment options involving adjunct antibiotics: 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 Tobramycin As a guide, intravenous (IV) injection over several minutes, OR an IV infusion over up to 1 hour. It may also be given by intramuscular (IM) injection. 2. Inhaled Tobramycin As a guide, Several formulations are used for inhalational therapy. Generally ampoules for nebulisation are used in preference to capsules for inhalation for PERIT. 500mg/5mL vial - (Tobra-Day); 300mg/5mL ampoule Tobramycin solution for inhalation (various brands), and 28mg capsules for inhalation (Tobi® Podhaler) which is PBS-subsidised for children greater than or equal to 6years old only. 3. No adjunct antibiotic 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 assigned arm the clinician is free to decide which therapy the participant shall be switched to. There will be no subsequent randomsiations to adjunct antibiotics 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 Adjunct antibiotic Domain. 3. Are eligible for at least two Interventions in the Adjunct Antibiotic Domain available at the clinical Site (including no Adjunct Antibiotic). 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 Adjunct Antibiotic Domain is not in their best interest. A participant will be excluded from Assignment to a specific Intervention in the Adjunct Antibiotic Domain if: 1. They have a known or suspected significant drug hypersensitivity to tobramycin or other aminoglycosides 2. Recognised contraindication to IV tobramycin, including known renal, auditory or vestibular impairment which, in the opinion of the Responsible Clinician, precludes its use. 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