| Title: |
Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials |
| Authors: |
Weiss,Emmanuel; Zahar,Jean-Ralph; Alder,Jeff; Asehnoune,Karim; Bassetti,Matteo; Bonten, Marc J. M.; Chastre,Jean; De Waele,Jan; Dimopoulos,George; Eggimann,Philippe; Engelhardt,Marc; Ewig,Santiago; Kollef,Marin; Lipman,Jeffrey; Luna,Carlos; Martin-Loeches,Ignacio; Pagani,Leonardo; Palmer,Lucy B.; Papazian,Laurent; Poulakou,Garyphallia; Prokocimer,Philippe; Rello,Jordi; Rex,John H.; Shorr,Andrew F.; Talbot,George H.; Thamlikitkul,Visanu; Torres,Antoni; Wunderink,Richard G.; Timsit,Jean-Francois; Epi Infectieziekten; MMB; Infection & Immunity; JC onderzoeksprogramma Infectious Diseases |
| Publication Year: |
2019 |
| Subject Terms: |
hospital-acquired bacterial pneumonia; multinational consensus; Delphi method; hierarchical composite endpoint; clinical cure; Taverne; Microbiology (medical); Infectious Diseases |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
1058-4838 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/389964 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/389964 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.37D20081 |
| Database: |
BASE |