Corresponding Author: Kasper Højgaard Thybo, MD, Department of Anesthesiology, Næstved Hospital, Ringstedgade 61, 4700 Næstved, Denmark (khty@regionsjealland.dk).
Accepted for Publication: December 26, 2018.
Author Contributions: Dr Thybo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Thybo and Hägi-Pedersen contributed equally to this article. Dr Mathiesen was senior author.
Concept and design: Thybo, Hägi-Pedersen, Dahl, Wetterslev, Mathiesen.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Thybo, Hägi-Pedersen, Dahl, Wetterslev, Skovmand, Mathiesen.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Thybo, Wetterslev, Jakobsen.
Obtained funding: Thybo, Dahl.
Administrative, technical, or material support: Thybo, Jakobsen, Overgaard, Schrøder, Bjørck, Skovmand, Frederiksen, Buus-Nielsen, Sørensen, Kruuse, Lindholm.
Supervision: Thybo, Hägi-Pedersen, Dahl, Pedersen, Overgaard, Bjørck, Skovmand, Lindholm, Mathiesen.
Other - Recruitment of participants and collection of data: Nersesjan.
Conflict of Interest Disclosures: Dr Thybo reported grants from the following: the Danish Society of Anaesthesiology and Intensive Care Medicine (DASAIM), Sophus Johansens Fund, Region Zealand Health Scientific Research Foundation, the local research foundation at Næstved-Slagelse-Ringsted Hospitals, the A.P. Møller Foundation for the Advancement of Medical Science, Aase og Ejnar Danielsens Fund, and the Grosserer Christian Andersen og Hustru Ingeborg Andersen, f. Schmidts legat (fund) during the conduct of the study; and was employed as a doctoral student while he was primary investigator of this trial. Dr Overgaard reported grants from Biomet Denmark, Biomet Inc, DePuy and Protesekompagniet, and Zimmer; serving as an investigator for Sanofi-Aventis Denmark A/S; and serving on an advisory board for Eli Lilly and Multipharma International Ltd outside the submitted work. No other disclosures were reported.
Funding/Support: Funding was provided by DASAIM, Sophus Johansens Fond, Region Zealand Health Scientific Research Foundation, the local research foundation at Næstved-Slagelse-Ringsted Hospitals, the A.P. Møller Foundation for the Advancement of Medical Science, Aase og Ejnar Danielsens Fond, and the Grosserer Christian Andersen og Hustru Ingeborg Andersen, f. Schmidts legat (fund).
Role of the Funder/Sponsor: None of the funders had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.
Additional Contributions: We wish to thank patients, relatives, and clinical and research staff at all trial sites. We give thanks to monitors for their excellent cooperation, in particular Birgitte Grøn, PhD, and Pernille Ask Aabo, MScPharm, at the Good Clinical Practice (GCP) unit at Copenhagen University Hospital, and Henriette Kunch Bendixen, MScPharm, at the GCP unit at Odense University Hospital. We also wish to thank Janus Engstrøm, BSc, at Copenhagen trial unit for creating and maintaining the trial database and creating the randomization list and allocation system. Finally, we wish to thank the Pharmacy of the Capital Region, Herlev for masking the trial medicine. Neither Grøn, Aabo, Bendixen, nor Engstrøm received personal compensation for their role in the trial.
Compensation for the Role in the Trial: The Copenhagen Trial Unit was paid for randomization and the electronic case report form. The GCP unit was compensated for monitoring the trial according to Danish law.
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