Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials

Emmanuel Weiss*, Jean Ralph Zahar, Jeff Alder, Karim Asehnoune, Matteo Bassetti, Marc J.M. Bonten, Jean Chastre, Jan De Waele, George Dimopoulos, Philippe Eggimann, Marc Engelhardt, Santiago Ewig, Marin Kollef, Jeffrey Lipman, Carlos Luna, Ignacio Martin-Loeches, Leonardo Pagani, Lucy B. Palmer, Laurent Papazian, Garyphallia PoulakouPhilippe Prokocimer, Jordi Rello, John H. Rex, Andrew F. Shorr, George H. Talbot, Visanu Thamlikitkul, Antoni Torres, Richard G. Wunderink, Jean François Timsit

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Randomized clinical trials (RCTs) in hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. Methods: Twenty-six international experts from intensive care, infectious diseases, and the pharmaceutical industry were polled using the Delphi method. Results: The panel recommended a hierarchical composite endpoint including, by priority order, (1) survival at day 28, (2) mechanical ventilation-free days through day 28, and (3) clinical cure between study days 7 and 10 for VABP; and (1) survival (day 28) and (2) clinical cure (days 7-10) for HABP. Clinical cure was defined as the combination of resolution of signs and symptoms present at enrollment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and mechanical ventilation-free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). Conclusions: We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials.

Original languageEnglish (US)
Pages (from-to)1912-1918
Number of pages7
JournalClinical Infectious Diseases
Volume69
Issue number11
DOIs
StatePublished - Nov 13 2019

Keywords

  • Delphi method
  • clinical cure
  • hierarchical composite endpoint
  • hospital-acquired bacterial pneumonia
  • multinational consensus

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials'. Together they form a unique fingerprint.

Cite this