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Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT

Scarborough, M; Li, HK; Rombach, I; Zambellas, R; Walker, AS; McNally, M; Atkins, B; ... Bejon, P; + view all (2019) Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT. Health Technology Assessment , 23 (38) 1-+. 10.3310/hta23380. Green open access

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Abstract

Background Management of bone and joint infection commonly includes 4–6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. Objective To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. Design Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. Setting Twenty-six NHS hospitals. Participants Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). Interventions Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. Main outcome measure The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. Results Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was –1.38% (90% confidence interval –4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. Limitations The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. Conclusions PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy.

Type: Article
Title: Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT
Open access status: An open access version is available from UCL Discovery
DOI: 10.3310/hta23380
Publisher version: https://doi.org/10.3310/hta23380
Language: English
Additional information: ll NIHR Journals Library reports have been produced under the terms of a commissioning contract issued by the Secretary of State for Health. Reports may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Permission to reproduce material from a published report is covered by the UK government’s non-commercial licence for public sector information. http://www.nationalarchives.gov.uk/doc/non-commercial-government-licence/version/2/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10079801
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