DOLPHIN
Trial question
What is the role of model-informed precision dosing of β-lactam antibiotics and ciprofloxacin in critically ill patients?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 388
388 patients (149 female, 239 male).
Inclusion criteria: adult patients admitted to the ICU who were treated with antibiotics.
Key exclusion criteria: pregnancy; antibiotic cessation before first blood sample collection; admittance for burn wounds, or receipt of study antibiotics as part of selective decontamination of digestive tract prophylaxis.
Interventions
N=189 model-informed precision dosing (individualized dose and interval adjustments based on monitoring serum drug levels combined with pharmacometric modeling of β-lactam antibiotics and ciprofloxacin).
N=199 standard dosing (antibiotic dosing based on local guidelines and freely adjusted by attending physician).
Primary outcome
Intensive care unit length of stay
10 days
8 days
10.0 days
7.5 days
5.0 days
2.5 days
0.0 days
Model-informed precision
dosing
Standard
dosing
No significant
difference ↔
No significant difference in ICU length of stay (10 days vs. 8 days; aIRR 1.16, 95% CI 0.96 to 1.41).
Secondary outcomes
No significant difference in the percentage of patients achieving target before intervention at day 1 (55.6% vs. 60.9%; aOR 0.78, 95% CI 0.52 to 1.18).
No significant difference in death in the ICU (21.7% vs. 18.1%; aOR 1.21, 95% CI 0.74 to 2.02).
No significant difference in death at day 28 (26.5% vs. 24.6%; aOR 1.04, 95% CI 0.65 to 1.66).
Safety outcomes
No significant difference in adverse events.
Conclusion
In adult patients admitted to the ICU who were treated with antibiotics, model-informed precision dosing was not superior to standard dosing with respect to ICU length of stay.
Reference
Tim M J Ewoldt, Alan Abdulla, Wim J R Rietdijk et al. Model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin in critically ill patients: a multicentre randomised clinical trial. Intensive Care Med. 2022 Dec;48(12):1760-1771.
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