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

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, J. Lipman, M. J. Llewelyn, S. Munoz-Price, M. Paul, A. Y. Peleg, J. Rodríguez-Baño, B. A. Rogers, H. Seifert, V. Thamlikitkul, G. ThwaitesS. Y. C. Tong, J. Turnidge, R. Utili, S. A. R. Webb, D. L. Paterson

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Abstract

Objectives: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). Methods: Prospective studies, randomized 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-centred clinical outcomes.

Original languageEnglish
Pages (from-to)533-541
JournalClinical Microbiology and Infection
Volume23
Issue number8
DOIs
Publication statusPublished - Aug 2017

Keywords

  • Antibiotic therapy
  • Bacteraemia
  • Bacterial infections
  • Clinical trials
  • Treatment outcome

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