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Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition

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posted on 2023-06-09, 03:58 authored by P N A Harris, J F McNamara, D C Lye, J S Davis, L Bernard, A C Cheng, Y Doi, V G Fowler, K S Kaye, L Leibovici, M J Lipman, Martin LlewelynMartin Llewelyn, S Munoz-Price, M Paul, A Y Peleg, J Rodríguez-Baño, B A Rogers, H Seifert, V Thamlikitkul, G Thwaites, S Y C Tong, J Turnidge, R Utili, S A R Webb, D L Paterson
Objectives: To define standardised endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infection (BSI). Methods: Prospective studies, randomised trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. Results: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically-confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically-confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. Conclusions: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centered clinical outcomes.


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Clinical Microbiology and Infection









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