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. Thwaites; S. Y. C. Tong; J. Turnidge; R. Utili; S. A. R. Webb; D. L. Paterson

doi:10.1016/j.cmi.2016.10.023

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

Research output: Contribution to journal › Article › Research › peer-review

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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 language	English
Pages (from-to)	533-541
Journal	Clinical Microbiology and Infection
Volume	23
Issue number	8
DOIs	https://doi.org/10.1016/j.cmi.2016.10.023
Publication status	Published - Aug 2017

Keywords

Antibiotic therapy
Bacteraemia
Bacterial infections
Clinical trials
Treatment outcome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmi.2016.10.023

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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., ... 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), 533-541. https://doi.org/10.1016/j.cmi.2016.10.023

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

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.",

keywords = "Antibiotic therapy, Bacteraemia, Bacterial infections, Clinical trials, Treatment outcome",

author = "Harris, {P. N A} and McNamara, {J. F.} and Lye, {D. C.} and Davis, {J. S.} and L. Bernard and Cheng, {A. C.} and Y. Doi and Fowler, {V. G.} and Kaye, {K. S.} and L. Leibovici and J. Lipman and Llewelyn, {M. J.} and S. Munoz-Price and M. Paul and Peleg, {A. Y.} and J. Rodr{\'i}guez-Ba{\~n}o and Rogers, {B. A.} and H. Seifert and V. Thamlikitkul and G. Thwaites and Tong, {S. Y. C.} and J. Turnidge and R. Utili and Webb, {S. A. R.} and Paterson, {D. L.}",

year = "2017",

month = aug,

doi = "10.1016/j.cmi.2016.10.023",

language = "English",

volume = "23",

pages = "533--541",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier",

number = "8",

}

Harris, PNA, McNamara, JF, Lye, DC, Davis, JS, Bernard, L, Cheng, AC, Doi, Y, Fowler, VG, Kaye, KS, Leibovici, L, Lipman, J, Llewelyn, MJ, Munoz-Price, S, Paul, M, Peleg, AY, Rodríguez-Baño, J, Rogers, BA, Seifert, H, Thamlikitkul, V, Thwaites, G, Tong, SYC, Turnidge, J, Utili, R, Webb, SAR & Paterson, DL 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

TY - JOUR

T1 - Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults

T2 - A consensus definition

AU - Harris, P. N A

AU - McNamara, J. F.

AU - Lye, D. 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 - Lipman, J.

AU - Llewelyn, M. J.

AU - Munoz-Price, S.

AU - Paul, M.

AU - Peleg, A. Y.

AU - Rodríguez-Baño, J.

AU - Rogers, B. A.

AU - Seifert, H.

AU - Thamlikitkul, V.

AU - Thwaites, G.

AU - Tong, S. Y. C.

AU - Turnidge, J.

AU - Utili, R.

AU - Webb, S. A. R.

AU - Paterson, D. L.

PY - 2017/8

Y1 - 2017/8

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.

AB - 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.

KW - Antibiotic therapy

KW - Bacteraemia

KW - Bacterial infections

KW - Clinical trials

KW - Treatment outcome

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U2 - 10.1016/j.cmi.2016.10.023

DO - 10.1016/j.cmi.2016.10.023

M3 - Article

AN - SCOPUS:85008255973

SN - 1198-743X

VL - 23

SP - 533

EP - 541

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 8

ER -

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

Abstract

Keywords

UN SDGs

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