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

Harris, P N A, McNamara, J F, Lye, D C, Davis, J S, Bernard, L, Cheng, A C, Doi, Y, Fowler, V G, Kaye, K S, Leibovici, L, Lipman, M J, Llewelyn, M J, Munoz-Price, S, Paul, M, Peleg, A Y, Rodríguez-Baño, J, Rogers, B A, Seifert, H, Thamlikitkul, V, Thwaites, G, Tong, S Y C, Turnidge, J, Utili, R, Webb, S A R and Paterson, D L (2017) Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition. Clinical Microbiology and Infection, 23 (8). pp. 533-541. ISSN 1198-743X

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Abstract

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.

Item Type: Article
Keywords: Antibiotic therapy; clinical trials; treatment outcome; bacteraemia; bacterial infections
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Depositing User: Sandy Gray
Date Deposited: 09 Nov 2016 11:34
Last Modified: 22 Aug 2017 16:28
URI: http://sro.sussex.ac.uk/id/eprint/65382

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