Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials.
- 2019
Available online from MWHC library: June 1997 - present, Available in print through MWHC library: 1999 - Winter 2007
Background: Randomized Clinical Trials (RCTs) in Hospital-Acquired (HABP) and Ventilator-Associated Bacterial Pneumonia (VABP) 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. Conclusion: 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. 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, for VABP (i) survival at day 28, (ii) mechanical ventilation (MV)-free-days through day 28, and (iii) clinical cure between study days 7 and 10; and for HABP (i) survival (day 28), and (ii) clinical cure (days 7-10). Clinical cure was defined as the combination of resolution of signs and symptoms present at enrolment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and MV-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).