| 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 JM; 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-François |
| Source: |
CLINICAL INFECTIOUS DISEASES ; ISSN: 1058-4838 ; ISSN: 1537-6591 |
| Publication Year: |
2019 |
| Collection: |
Ghent University Academic Bibliography |
| Subject Terms: |
Medicine and Health Sciences; hospital-acquired bacterial pneumonia; multinational consensus; Delphi method; hierarchical composite endpoint; clinical cure; VENTILATOR-ASSOCIATED PNEUMONIA; INFECTIONS; DURATION |
| 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: |
application/pdf |
| Language: |
English |
| Relation: |
https://biblio.ugent.be/publication/8599598; https://doi.org/10.1093/cid/ciz093; https://biblio.ugent.be/publication/8599598/file/8599606; https://biblio.ugent.be/publication/8599598/file/8656412 |
| DOI: |
10.1093/cid/ciz093 |
| Availability: |
https://biblio.ugent.be/publication/8599598; https://hdl.handle.net/1854/LU-8599598; https://doi.org/10.1093/cid/ciz093; https://biblio.ugent.be/publication/8599598/file/8599606; https://biblio.ugent.be/publication/8599598/file/8656412 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.9A8E539F |
| Database: |
BASE |