TARGET (therapeutic drug monitoring)
Trial question
Is therapeutic drug monitoring superior to continuous infusion of piperacillin/tazobactam in patients with sepsis?
Study design
Multi-center
Single blinded
RCT
Population
Characteristics of study participants
31.0% female
69.0% male
N = 249
249 patients (77 female, 172 male)
Inclusion criteria: adult patients with sepsis
Key exclusion criteria: contraindications to the study drug; impaired liver function; palliative care only; pregnancy; first measurement of piperacillin concentration not possible within 24 hours after randomization
Interventions
N=125 therapeutic drug monitoring (continuous infusion with dosing guided by daily therapeutic drug monitoring of piperacillin)
N=124 fixed dose (continuous infusion with a fixed dose of 13.5 g/day)
Primary outcome
Mean of daily total sequential organ failure assessment score up to day 10
7.9
8.2
8.2 points
6.1 points
4.1 points
2.0 points
0.0 points
Therapeutic drug
monitoring
Fixed
dose
No significant
difference ↔
No significant difference in mean of daily total SOFA score up to day 10 (7.9 points vs. 8.2 points; AD 0.3 points, 95% CI -0.4 to 1)
Secondary outcomes
No significant difference in death at day 28 (21.6% vs. 25.8%; RR 0.8, 95% CI 0.5 to 1.3)
No significant difference in clinical cure (35.6% vs. 17.4%; OR 1.9, 95% CI 0.5 to 6.2)
No significant difference in microbiological cure (56.3% vs. 46%; OR 2.4, 95% CI 0.7 to 7.4)
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult patients with sepsis, therapeutic drug monitoring was not superior to fixed dose with respect to mean of daily total SOFA score up to day 10.
Reference
Stefan Hagel, Friedhelm Bach, Thorsten Brenner et al. Effect of therapeutic drug monitoring-based dose optimization of piperacillin / tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial. Intensive Care Med. 2022 Mar;48(3):311-321.
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