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(1): 330, 2019 Jun 06.
Article
em En
| MEDLINE
| ID: mdl-31171029
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. TRIAL REGISTRATION German Clinical Trials Register (GermanCTR), DRKS00011159 . Registered on 10 October 2016.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Promover_ampliacao_atencao_especializada
Contexto em Saúde:
4_TD
Base de dados:
MEDLINE
Assunto principal:
Monitoramento de Medicamentos
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Sepse
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Combinação Piperacilina e Tazobactam
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Antibacterianos
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Guideline
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Observational_studies
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Prognostic_studies
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Qualitative_research
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Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Trials
Ano de publicação:
2019
Tipo de documento:
Article