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Therapeutic Monitoring of Beta-lactams in Critically Ill Patients With Sepsis

ConditionBacterial Sepsis
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorComplexo Hospitalario Universitario de A Coruña

About this trial

Background: Sepsis is a leading cause of morbidity and mortality among critically ill patients and is associated with intensive use of β-lactam antibiotics. These drugs show time-dependent pharmacodynamics and high pharmacokinetic variability in this population, making it difficult to achieve therapeutic levels. Therapeutic drug monitoring (TDM) may optimize dosing, but its routine clinical implementation remains limited.

Objective: To evaluate whether individualized β-lactam dosing guided by TDM reduces time to full clinical recovery compared with standard dosing in critically ill patients with sepsis.

Methods: OPTIBETA is a pragmatic, randomized, controlled, open-label clinical trial to be conducted at a tertiary hospital in Spain. Adult patients (≥18 years) admitted to the intensive care unit or infectious diseases ward with sepsis will be included. Participants will be randomized 1:1 to either a TDM-guided dosing arm (dose adjustments according to PK/PD targets) or a standard dosing arm. Clinical, microbiological, and pharmacological outcomes will be collected. The primary endpoint is time to complete clinical cure. Secondary outcomes include overall survival, microbiological cure, ICU and hospital length of stay, adverse events, and achievement of PK/PD targets. The estimated sample size is 198 patients.

Expected results: We hypothesize that TDM-guided dosing will reduce time to clinical cure, improve overall outcomes, and decrease adverse events compared with standard dosing.

Conclusions: OPTIBETA will provide high-quality evidence on the role of β-lactam TDM in critically ill septic patients and may support its inclusion in antimicrobial stewardship programs.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years.

Diagnosis of sepsis according to Sepsis-3 (SOFA ≥2).

Initiation of treatment with beta-lactam antibiotics.

Informed consent signed by the patient or their legal representative within the first 48 hours after the start of antibiotic therapy.

Disqualifiers

Pregnancy or breastfeeding.

Known hypersensitivity to beta-lactams.

Discontinuation of antibiotic treatment before the first TDM determination.

Simultaneous participation in another clinical trial.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Individualized dosing of beta-lactam antibiotics based on therapeutic monitoring

    Other intervention

    In the intervention group, plasma levels will be determined 48 hours after the start of antibiotic treatment and subsequently every 4-5 days, with a pharmacotherapeutic report and dosage adjustment within \<24 hours. In the control group, samples will be stored at -80 °C and analyzed at the end of the study, with no impact on clinical practice. Plasma concentrations of beta-lactam antibiotics will be determined by high-performance liquid chromatography (HPLC) using validated commercial kits, which allow simultaneous quantification of several drugs in this group with reduced processing times and feasible implementation in hospital routine. Patients will be evaluated weekly until hospital discharge, death, or completion of antibiotic treatment. Clinical progression, inflammatory markers, emergence of resistance, adverse effects, and clinical and microbiological outcomes will be recorded.

Treatment groups

198 Participants
are divided into 2 treatment groups
Group A: Intervention group (individualized dosing based on therapeutic monitoring)Experimental treatment 1 intervention
Group B: Control group (usual dosage):No intervention 0 interventions

Trial outcomes

Primary outcomes

1

Time to complete clinical cure

The primary endpoint will be the time to complete clinical cure, defined as resolution of signs and symptoms of infection, functional recovery, baseline or improved SOFA score (≥2 points from baseline), and no need to initiate new antibiotic treatment.

Time frame
From the date of randomization to the date of clinical cure, assessed every 7 days and until the end of the study, an average of 3 years.

Secondary outcomes

1

Time to microbiological cure (negative cultures).

Time until microbiological cultures become negative

Time frame
From the date of randomization to the date of microbiological cure, assessed every 7 days and until the end of the study, an average of 3 years
2

Overall survival (OS)

Length of time that patients remain alive after start of treatment.

Time frame
From the start date of treatment until the end of the study, an average of 3 years.
3

Length of hospital stay

Number of days the patient remains hospitalized

Time frame
From the date of randomization until the end of the study, an average of 3 years.
4

Number of days free of life support

Number of days free of life support (vasopressors, renal replacement therapy, extracorporeal membrane oxygenation).

Time frame
From the date of randomization until the end of the study, an average of 3 years.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Complexo Hospitalario Universitario de A Coruña

Lead sponsor

Hospital Clínico Universitario de Santiago de Compostela

Collaborator

Source ClinicalTrials.gov

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