Hagel, Stefan ORCID: 0000-0003-2999-6131, Fiedler, Sandra, Hohn, Andreas, Brinkmann, Alexander, Frey, Otto R., Hoyer, Heike, Schlattmann, Peter, Kiehntopf, Michael, Roberts, Jason A., Pletz, Mathias W., Bloos, Frank, Angermair, Stefan, Bracht, Hendrik, Barth, Eberhard, Kluge, Stefan, Nierhaus, Axel, Motsch, Johann, Brenner, Thorsten, Annecke, Thorsten ORCID: 0000-0002-2496-4432, Bach, Friedhelm, Weigand, Markus, Schappacher, Markus, von Ameln-Mayerhofer, Andreas, Michels, Guido, Roehr, Anka, Fuchs, Thomas, Eichner, Sarah, Barth, Eberhard, Kong, Christina, Pinder, Nadine, Mueller, Carsten, Petersen, Miriam, Schlattmann, Peter, Steinbach, Gerald, Jarczak, Dominik, Weisman, Dirk, Kurlbaum, Max and Braune, Anke (2019). Therapeutic drug monitoring-based dose optimisation of piperacillin/tazobactam to improve outcome in patients with sepsis (TARGET): a prospective, multi-centre, randomised controlled trial. Trials, 20. LONDON: BMC. ISSN 1745-6215

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Abstract

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection with a hospital mortality in excess of 40%. Along with insufficient and delayed empirical antimicrobial therapy, inappropriate antimicrobial exposure has been identified to negatively affect patient outcomes. Receipt of prolonged infusion (i.e. extended or continuous infusion) of piperacillin/tazobactam (TZP) improves antimicrobial exposure and is associated with reduced mortality in patients with sepsis. Using therapeutic drug monitoring (TDM) with dosing tailored to the altered pharmacokinetics of the individual patient to avoid under-and overdosing may be a further strategy to improve patient outcomes. This current trial will address the question whether a TDM-guided therapy with TZP administered by continuous infusion will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion of the total daily dose of TZP without TDM. Methods: The study is an investigator-initiated, multi-centre, parallel-group, single-blinded, randomised controlled trial. The trial will be conducted in several centres across Germany. Adult patients (aged >= 18 years) with severe sepsis or septic shock will be eligible for study participation. Participants will be randomly assigned to receive either TZP by continuous infusion guided by daily TDM of piperacillin (experimental group) or by continuous infusion without TDM guidance (total daily dose in normal renal function 13.5 g TZP) (control group). The pharmacokinetic (PK)/ pharmacodynamic (PD) target will be 100% f T->4MIC (percentage of time during a dosing interval that the free [f] drug concentration exceeds 4 times the minimum inhibitory concentration). The primary efficacy endpoint is the change in mean total Sequential Organ Failure Assessment score from day 1 after randomisation until day 10 or discharge from the intensive care unit or death, whichever comes first. Secondary outcomes include mortality, clinical cure, microbiological cure, overall antibiotic use, individual components of the primary outcome, adverse events and analysis of PK and (PD) indices. Discussion: This trial will assess for the first time whether continuous infusion of TZP guided by daily TDM in patients with sepsis will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion without TDM.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hagel, StefanUNSPECIFIEDorcid.org/0000-0003-2999-6131UNSPECIFIED
Fiedler, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohn, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinkmann, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frey, Otto R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyer, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlattmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiehntopf, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roberts, Jason A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pletz, Mathias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloos, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angermair, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bracht, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barth, EberhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluge, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nierhaus, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Motsch, JohannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Annecke, ThorstenUNSPECIFIEDorcid.org/0000-0002-2496-4432UNSPECIFIED
Bach, FriedhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weigand, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schappacher, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Ameln-Mayerhofer, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michels, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roehr, AnkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuchs, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichner, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barth, EberhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kong, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pinder, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, MiriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlattmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinbach, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jarczak, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weisman, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurlbaum, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braune, AnkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-138058
DOI: 10.1186/s13063-019-3437-x
Journal or Publication Title: Trials
Volume: 20
Date: 2019
Publisher: BMC
Place of Publication: LONDON
ISSN: 1745-6215
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CRITICALLY-ILL PATIENTS; DEFINING ANTIBIOTIC LEVELS; BETA-LACTAM ANTIBIOTICS; CARE-UNIT PATIENTS; PROLONGED INFUSION; MEROPENEM; PHARMACOKINETICS; FAILURE; SCOREMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13805

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