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  • 1
    In: BMJ Open, BMJ, Vol. 12, No. 12 ( 2022-12), p. e065401-
    Abstract: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy. Methods and analysis We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia’s Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50–100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with 〉 80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics. Ethics and dissemination Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children’s Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website ( https://www.phageaustralia.org/ ). Trial registration number Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2599832-8
    Location Call Number Limitation Availability
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  • 2
    In: BMJ Open, BMJ, Vol. 11, No. 3 ( 2021-03), p. e046142-
    Abstract: Antimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs. Methods and analysis The START trial will implement and evaluate a nurse-led AMS programme via a stepped-wedge cluster randomised controlled trial design in 12 RACFs over 16 months. The AMS programme will incorporate education, aged care-specific treatment guidelines, documentation forms, and audit and feedback strategies that will target aged care staff, general practitioners, pharmacists, and residents and their families. The intervention will primarily focus on urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections. RACFs will transition from control to intervention phases in random order, two at a time, every 2 months, with a 2-month transition, wash-in period. The primary outcome is the cumulative proportion of residents within each facility prescribed an antibiotic during each month and total days of antibiotic use per 1000 occupied bed days. Secondary outcomes include the number of courses of systemic antimicrobial therapy, antimicrobial appropriateness, antimicrobial resistant organisms, Clostridioides difficile infection, change in antimicrobial susceptibility profiles, hospitalisations and all-cause mortality. Analyses will be conducted according to the intention-to-treat principle. Ethics and dissemination Ethics approval has been granted by the Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/591). Research findings will be disseminated through peer-reviewed publications, conferences and summarised reports provided to participating RACFs. Trial registration number NCT03941509 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2599832-8
    Location Call Number Limitation Availability
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