Members of the PRÄP-GO consortium are: Charité – Universitätsmedizin Berlin (executing entity: Department of Anesthesiology and Operative Intensive Care Medicine (CVK/CCM), Prof. Dr. med. Claudia Spies), BARMER health insurance (executing entity: Intitute for health system research, Dr. med. Ursula Marschall), St. Joseph Krankenhaus Berlin-Tempelhof GmbH (executing entity: Clinic for Geriatrics, Dr. med. Rahel Eckardt-Felmberg; Hausarztpraxis Landgraf (Dr. med Irmgard Landgraf), Brandenburg Medical School Theodor Fontane (executing entity: Institute of General medicine, Prof. Dr. med. Ulrich Schwantes), Technische Universität Berlin (executing entity: Department of Healthcare Management, Prof. Dr. med. Reinhard Busse), Ludwig-Maximilians-Universität München (executing entity: Institute for Medical Information Processing, Biometry, and Epidemiology, Prof. Dr. rer. nat. Ulrich Mansmann).
The PRÄP-GO investigators can be found in Additional File 1.
The PRÄPGO trial study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) . The SPIRIT checklist is included in Additional File 2. The SPIRIT figure is Additional File 4.
The PRÄP-GO consortium members applied for funding of the project and built the legal representation of the project. CS is the principal investigator; she conceived the study, led the proposal and protocol development. SJS is her deputy, he contributed to the study design and protocol development. KS is the study coordinator; she contributed to the study design and protocol development. UM is the independent study statistician, he contributed to the study proposal and protocol development. RB, WQ and TR are responsible for the health economic evaluation. CS, SJS, KS, RM and JK represent the management committee of PRÄPGO and were involved in the protocol development and in ethical approval. VL supervises the randomization, is involved in the data management (quality checks) and contributes to the project management.
SJS and JK drafted the manuscript. All authors critically revised the manuscript and approved its final version.
The trial is funded by a grant obtained by the PRÄP-GO consortium via the “Innovationsauschuss” of the Federal Joint Committee (G-BA), which is the highest decision-making body of the joint self-government of physicians, dentists, hospitals, and health insurance funds in Germany (https://www.g-ba.de/english/), funding permit number 01NVF18024. A translated copy of the original funding documentation can be found in Additional file 6.
The G-BA had no role in study design; collection, management, analysis, and interpretation of data, writing of the report; and the decision to submit the report for publication.
Availability of data and materials
The Institute for Medical Information Processing, Biometray, and Epidemiology of the Ludwig-Maximilian University Munich will handle the randomization as well as the data analysis. The health care economic evaluation will be performed by the Department of Healthcare Management of the Technische Universität Berlin. The study database, monitoring, and safety reporting are operated by the Department of Anesthesiology and Operative Intensive Care of the Charité – Universitätsmedizin Berlin. Regularly safety reports are generated and distributed to the Data Safety and Monitoring Committee. De-identified datasets can be made available on reasonable scientific request to the management committee after the primary publication. Access might be restricted due to German data protection laws.
Ethical approval and consent to participate
The study has been approved by the ethical committee of the Charité – Universitätsmedizin Berlin as the primary study centre (approval number EA1/225/19, see Additional File 7). Any participation study centre will either join the ethical approval of the Charité or, if needed, will have the study approved by the respective responsible ethical committee before starting to include patients. The study is registered at ClinicalTrials.gov with the trial registry number NCT04418271 and has the Universal Trial Number (UTN) U1111-1253-4820. The current study protocol is version 1.1 (13.06.2020). The trial will be conducted in agreement with the principles of the Declaration of Helsinki. All participants will be informed about the purpose of the trial, the risks, and the potential benefits. There is no anticipated harm and compensation for trial participation. Written informed consent will be obtained by the local study physician from each participant. The Department of Anesthesiology and Operative Intensive Care Medicine of the Charité – Universitätsmedizin Berlin coordinates the study. The original study protocol (in German) and the statistical analysis plan including amendments are publicly available at www.praep-go.de.
Any changes to the protocol that affect or could affect the study design or procedures, the objectives and hypotheses, or patient safety must be submitted as an amendment to the ethics committees of the study centres for consultation. The new version of the study protocol will be made available at the project’s website, including the rationale for any changes. The Clinical Trials entry will be adjusted if necessary.
Minor changes, such as organisational adjustments, changes in written manuals for the pure reason of clarification of any processes, or changes in responsibilities that have no effects on the defined study goals and conduction, will be agreed upon by the management committee of PRAEP-GO. In such cases, the ethical committee of the leading study centre will be notified of such changes.
Consent for publication
SJ Schaller reports personal fees for educational purposes from Springer Verlag GmbH (Vienna, Austria) and for lectures from Fresenius (Bad Homburg, Germany), grants and non-financial support from ESICM (Brussels, Belgium), Fresenius (Bad Homburg, Germany), STIMIT AG (Biel, Switzerland), and Reactive Robotics GmbH (Munich, Germany) as well as from national (e.g. DGAI) and international (e.g. ESICM) medical societies (or their congress organizers) in the field of anesthesiology and intensive care, all outside the submitted work; SJS holds stocks in small amounts from Alphabeth Inc., Bayer AG, Rhön-Klinikum AG, and Siemens AG. These did not have any influence on this study.
J Kiselev reports no competing interests.
V Loidl reports no competing interests.
W Quentin reports no competing interests.
K Schmidt reports no competing interests.
R Mörgeli reports no competing interests.
T Rombey received honorary fees for commissioned research by the Statutory Health Insurance Medical Review Board R Busse reports no competing interests.
U Mannsmann reports no competing interests.
C Spies reports grants from Gemeinsamer Bundesausschuss / Federal Joint Committee (G-BA) during the conduct of the study, grants from BMG / RKI, grants from Deutsche Forschungsgemeinschaft / German Research Society, grants from Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) /German Aerospace Center, grants from Einstein Stiftung Berlin/ Einstein Foundation Berlin, grants from Inneruniversitäre Forschungsförderung / Inner University Grants, grants from Projektträger im DLR / Project Management Agency, grants from Stifterverband/Non-Profit Society Promoting Science and Education, grants from European Society of Anaesthesiology and Intensive Care, grants from Baxter Deutschland GmbH, grants from Cytosorbents Europe GmbH, grants from Edwards Lifesciences Germany GmbH, grants from Fresenius Medical Care, grants from Grünenthal GmbH, grants from Masimo Europe Ltd., grants from Pfizer Pharma PFE GmbH, personal fees from Georg Thieme Verlag, grants from Dr. F. Köhler Chemie GmbH, grants from Sintetica GmbH, grants from Stifterverband für die deutsche Wissenschaft Þ.V. / PhilipsÐ grants from Stiftung Charité, grants from AGUETTANT Deutschland GmbH, grants from AbbVie Deutschland GmbH & Co. KG, grants from Amomed Pharma GmbH, grants from InTouch Health, grants from Copra System GmbH, grants from Correvio GmbH, grants from Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., grants from Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin (DGAI, grants from Stifterverband für die deutsche Wissenschaft Þ.V. / Metronic, grants from Philips ElectronicsNederland BV, grants from BMG / RKI, grants from BMBF, grants from BMBF, grants from Deutsche Forschungsgemeinschaft / German Research Society, grants from Drägerwerk AG & Co. KGaA, outside the submitted work; In addition, Dr. Spies has a patent 10 2014 215 211.9 licensed, a patent 10 2018 114 364.8 licensed, a patent 10 2018 110 275.5 licensed, a patent 50 2015 010 534.8Ðlicensed, a patent 50 2015 010 347.7 licensed, and a patent 10 2014 215 212.7 licensed.