Core Outcome Measures in Effectiveness Trials

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

General Information

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.

Authors:
Harris, P. N. A. McNamara, J. F. Lye, D. C. Davis, J. S. Bernard, L. Cheng, A. C. Doi, Y. Fowler, V. G., Jr. Kaye, K. S. Leibovici, L. Lipman, J. Llewelyn, M. J. Munoz-Price, S. Paul, M. Peleg, A. Y. Rodriguez-Bano, 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.

Publication

Journal:
Clin Microbiol Infect
Volume:
23
Issue:
8
Pages:
533 - 541
Year:
2017
DOI:
Further Study Information

Date:
Funding source(s):

Health Area

Disease Category
Infectious disease

Disease Name
Bloodstream infections

Target Population

Age Range
18 - 100

Sex
Either


Nature / type of Intervention
Drug

Method(s)

Focus group(s)
Systematic review

Stakeholders Involved

Clinical experts
Researchers
Statisticians

Study Type

COS for clinical trials or clinical research

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