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. L. Paterson, P. N.A. Harris, J. F. McNamara, D. C. Lye, J. S. Davis, S. Y.C. Tong, J. S. Davis, L. Bernard, A. C. Cheng, Y. Doi, V. G. Fowler, K. S. Kaye, L. Leibovici, L. Leibovici, J. Lipman, J. Lipman, Luisa Munoz-Price, M. J. LlewelynS. Munoz-Price, M. Paul, A. Y. Peleg, A. Y. Peleg, B. A. Rogers, J. Rodríguez-Baño, H. Seifert, H. Seifert, V. Thamlikitkul, G. Thwaites, G. Thwaites, J. Turnidge, R. Utili, S. A.R. Webb

Research output: Contribution to journalShort survey

19 Citations (Scopus)

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 (US)
Pages (from-to)533-541
Number of pages9
JournalClinical Microbiology and Infection
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Fingerprint

Clinical Trials
Infection
Organ Dysfunction Scores
Staphylococcus aureus
Survival
Fever
Anti-Bacterial Agents
Prospective Studies
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

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.; Paterson, D. L.; Harris, P. N.A.; McNamara, J. F.; Lye, D. C.; Davis, J. S.; Tong, S. Y.C.; Davis, J. S.; Bernard, L.; Cheng, A. C.; Doi, Y.; Fowler, V. G.; Kaye, K. S.; Leibovici, L.; Leibovici, L.; Lipman, J.; Lipman, J.; Munoz-Price, Luisa; Llewelyn, M. J.; Munoz-Price, S.; Paul, M.; Peleg, A. Y.; Peleg, A. Y.; Rogers, B. A.; Rodríguez-Baño, J.; Seifert, H.; Seifert, H.; Thamlikitkul, V.; Thwaites, G.; Thwaites, G.; Turnidge, J.; Utili, R.; Webb, S. A.R.

In: Clinical Microbiology and Infection, Vol. 23, No. 8, 01.08.2017, p. 533-541.

Research output: Contribution to journalShort survey

Harris, PNA, McNamara, JF, Paterson, DL, Harris, PNA, McNamara, JF, Lye, DC, Davis, JS, Tong, SYC, Davis, JS, Bernard, L, Cheng, AC, Doi, Y, Fowler, VG, Kaye, KS, Leibovici, L, Leibovici, L, Lipman, J, Lipman, J, Munoz-Price, L, Llewelyn, MJ, Munoz-Price, S, Paul, M, Peleg, AY, Peleg, AY, Rogers, BA, Rodríguez-Baño, J, Seifert, H, Seifert, H, Thamlikitkul, V, Thwaites, G, Thwaites, G, Turnidge, J, Utili, R & Webb, SAR 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, vol. 23, no. 8, pp. 533-541. https://doi.org/10.1016/j.cmi.2016.10.023
Harris, P. N.A. ; McNamara, J. F. ; Paterson, D. L. ; Harris, P. N.A. ; McNamara, J. F. ; Lye, D. C. ; Davis, J. S. ; Tong, S. Y.C. ; Davis, J. S. ; Bernard, L. ; Cheng, A. C. ; Doi, Y. ; Fowler, V. G. ; Kaye, K. S. ; Leibovici, L. ; Leibovici, L. ; Lipman, J. ; Lipman, J. ; Munoz-Price, Luisa ; Llewelyn, M. J. ; Munoz-Price, S. ; Paul, M. ; Peleg, A. Y. ; Peleg, A. Y. ; Rogers, B. A. ; Rodríguez-Baño, J. ; Seifert, H. ; Seifert, H. ; Thamlikitkul, V. ; Thwaites, G. ; Thwaites, G. ; Turnidge, J. ; Utili, R. ; Webb, S. A.R. / Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults : a consensus definition. In: Clinical Microbiology and Infection. 2017 ; Vol. 23, No. 8. pp. 533-541.
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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.",
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T2 - a consensus definition

AU - Harris, P. N.A.

AU - McNamara, J. F.

AU - Paterson, D. L.

AU - Harris, P. N.A.

AU - McNamara, J. F.

AU - Lye, D. C.

AU - Davis, J. S.

AU - Tong, S. Y.C.

AU - Davis, J. S.

AU - Bernard, L.

AU - Cheng, A. C.

AU - Doi, Y.

AU - Fowler, V. G.

AU - Kaye, K. S.

AU - Leibovici, L.

AU - Leibovici, L.

AU - Lipman, J.

AU - Lipman, J.

AU - Munoz-Price, Luisa

AU - Llewelyn, M. J.

AU - Munoz-Price, S.

AU - Paul, M.

AU - Peleg, A. Y.

AU - Peleg, A. Y.

AU - Rogers, B. A.

AU - Rodríguez-Baño, J.

AU - Seifert, H.

AU - Seifert, H.

AU - Thamlikitkul, V.

AU - Thwaites, G.

AU - Thwaites, G.

AU - Turnidge, J.

AU - Utili, R.

AU - Webb, S. A.R.

PY - 2017/8/1

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N2 - 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.

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KW - Bacteraemia

KW - Bacterial infections

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KW - Treatment outcome

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