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

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.

• Authors: 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 Poulakou, Philippe Prokocimer, Jordi Rello, John H Rex, Andrew F Shorr, George H Talbot, Visanu Thamlikitkul, Antoni Torres, Richard G Wunderink, Jean-François Timsit
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 69 Issue 11 Pg. 1912-1918 (11 13 2019) ISSN: 1537-6591 [Electronic] United States
• PMID: 30722013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents

Topics

• Anti-Bacterial Agents (therapeutic use)
• Consensus
• Critical Care (methods)
• Cross Infection (drug therapy, microbiology)
• Humans
• Pneumonia, Bacterial (drug therapy, microbiology)
• Pneumonia, Ventilator-Associated (drug therapy, microbiology)
• Treatment Outcome