Elaboration of Consensus Clinical Endpoints to Evaluate Antimicrobial Treatment Efficacy in Future Hospital-acquired/Ventilator-associated Bacterial Pneumonia Clinical Trials.
- Weiss E Department of Anesthesiology and Critical Care, Assistance Publique-Hôpitaux de Paris (AP-HP), Beaujon Hospital, Clichy.
- Zahar JR Department of Clinical Microbiology and Infection Control Unit, Avicennes Hospital, AP-HP, Bobigny.
- Alder J Bayer US LLC, Parsippany, New Jersey.
- Asehnoune K University Hospital of Nantes, Intensive Care Unit, Anesthesia and Critical Care Department, Hôtel Dieu, Nantes, France.
- Bassetti M Infectious Diseases Division, Department of Medicine, University of Udine and Santa Maria Misericordia University Hospital, Italy.
- Bonten MJM Department of Medical Microbiology and Julius Center for Health Science and Primary Care, University Medical Center Utrecht, The Netherlands.
- Chastre J Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
- De Waele J Department of Critical Care Medicine, Ghent University Hospital, Belgium.
- Dimopoulos G Department of Critical Care, University Hospital Attikon, National and Kapodistrian University of Athens, Greece.
- Eggimann P Department of Critical Care, Centre Hospitalier Universitaire Vaudois, Lausanne.
- Engelhardt M Basilea Pharmaceutica International Ltd, Basel, Switzerland.
- Ewig S Department of Respiratory Medicine and Infectious Diseases, Evangelic Hospital in Herne and Augusta Hospital, Bochum, Germany.
- Kollef M Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, Missouri.
- Lipman J Royal Brisbane and Womens Hospital, Australia.
- Luna C Department of Medicine, Pulmonary Diseases Division, Hospital de Clínicas, Universidad de Buenos Aires, Argentina.
- Martin-Loeches I Department of Clinical Medicine, Multidisciplinary Intensive Care Research Organization, St James's Hospital, Trinity Centre for Health Sciences, Dublin, Ireland.
- Pagani L Infectious Diseases Unit, Bolzano Central Hospital, Italy.
- Palmer LB Pulmonary, Critical Care and Sleep Division, State University of New York at Stony Brook, France.
- Papazian L Médecine Intensive-Réanimation, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, France.
- Poulakou G Third Department of Medicine, Sotiria General Hospital, Greece.
- Prokocimer P Merck & Co, Inc, Kenilworth, New Jersey.
- Rello J Centro Investigacion Biomedica En Red de Enfermedades Respiratorias (CIBERES), Vall d'Hebron Barcelona Hospital Campus, Spain.
- Rex JH F2G, Ltd, Eccles, United Kingdom.
- Shorr AF Medstar Washington Hospital Center, Washington, District of Columbia.
- Talbot GH Talbot Advisors LLC, Anna Maria, Florida.
- Thamlikitkul V Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
- Torres A Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Institut De Investigacio Biomedica Agusti Pi i Sunyer, CIBERES, Spain.
- Wunderink RG Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
- Timsit JF AP-HP, Medical and Infectious Diseases Intensive Care Unit, Bichat Hospital, Paris.
- 2019-02-06
Published in:
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - 2019
Delphi method
clinical cure
hierarchical composite endpoint
hospital-acquired bacterial pneumonia
multinational consensus
Anti-Bacterial Agents
Consensus
Critical Care
Cross Infection
Humans
Pneumonia, Bacterial
Pneumonia, Ventilator-Associated
Treatment Outcome
English
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.
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1093/cid/ciz093
- PMID 30722013
- Persistent URL
- https://folia.unifr.ch/global/documents/295903
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