Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition. (August 2017)

• Record Type: Journal Article
• Authors: 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, 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.; Paterson, D.L.
• Is Part Of: Clinical microbiology and infection. Volume 23:Number 8(2017)
• Page Start: 533
• Page End: 541
• Publication Date: 2017-08
• Subjects: Antibiotic therapy -- Bacteraemia -- Bacterial infections -- Clinical trials -- Treatment outcome; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2016.10.023
• Languages: English
• ISSNs: 1198-743X

Abstract

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.