Bacterial SepsisNCT07270523
Therapeutic Monitoring of Beta-lactams in Critically Ill Patients With Sepsis
A study testing Individualized dosing of beta-lactam antibiotics based on therapeutic monitoring in people with Bacterial Sepsis, run by Complexo Hospitalario Universitario de A Coruña at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Sepsis
- What is being tested?
- Individualized dosing of beta-lactam antibiotics based on therapeutic monitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2026to 1 Jan 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Pregnancy or breastfeeding.
- Known hypersensitivity to beta-lactams.
- Discontinuation of antibiotic treatment before the first TDM determination.
- Simultaneous participation in another clinical trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Manuel A Gómez-Rios, Anesthesiologist contact
Spain1 site
Clinical Hospital of Santiago de Compostela
Santiago de Compostela, A Coruña, 15705
Iria Varela Rey, Pharmacist, 697538722, iriavarela13@gmail.com
About this study
Official title: Therapeutic Monitoring of Beta-lactams in Critically Ill Patients With Sepsis: OPTIBETA Clinical Trial Protocol
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.
Read more
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.
Read the detailed description
Sepsis is a global health problem of enormous magnitude, responsible for more than 48 million cases and 11 million deaths annually, accounting for around 20% of global mortality. Its prevalence is particularly high in critically ill patients, occurring in up to 40% of ICU admissions. In Spain, it causes more than 17,000 deaths per year, exceeding the mortality rate of some types of cancer. In addition to its clinical impact, sepsis entails a considerable economic burden, with direct costs estimated at between €20,000 and €30,000 per patient admitted to the ICU, to which must be added indirect costs arising from functional sequelae and loss of productivity. Early and appropriate antibiotic treatment is essential to improve prognosis, with beta-lactam antibiotics being the most widely used group due to their broad spectrum of action and safety profile. These drugs have time-dependent pharmacodynamics and high pharmacokinetic variability in septic patients, conditioned by factors such as multiple organ dysfunction, increased distribution volume, and renal hyperfiltration. These alterations make it difficult to achieve adequate therapeutic concentrations and can lead to both underdosing-associated with therapeutic failure and the development of resistance-and overdosing, with an increased risk of toxicity, especially neurological toxicity. These alterations make it difficult to achieve adequate therapeutic concentrations and can lead to both underdosing-associated with therapeutic failure and the development of resistance-and overdosing, with an increased risk of toxicity, especially neurological toxicity.
Therapeutic drug monitoring (TDM) applied to beta-lactam antibiotics allows for individualized dosage adjustment based on pharmacokinetic/pharmacodynamic (PK/PD) targets. Despite strong observational evidence supporting this strategy, its clinical implementation remains limited due to technical, organizational, and economic barriers, and the absence of pragmatic randomized clinical trials makes it difficult to establish its true impact on healthcare practice.
In this context, the OPTIBETA project hypothesizes that personalized dosing of beta-lactam antibiotics guided by MDT improves time to clinical cure compared to standard dosing in critically ill patients with sepsis. The primary objective of this trial is to evaluate the efficacy of individualized dosing based on MDT versus the conventional regimen in terms of reducing the time to complete clinical cure.
Hypothesis:
The administration of beta-lactam antibiotics adjusted to PK/PD targets in critically ill patients with sepsis based on plasma level determination improves clinical and microbiological cure compared to standard dosing.
Objectives:
The overall objective is to evaluate the efficacy and safety of personalized dosing of beta-lactam antibiotics based on TDM, compared to standard dosing, in critically ill patients with sepsis.
- Primary objective Evaluate whether individualized dosing of beta-lactam antibiotics based on pharmacokinetic monitoring and achievement of PK/PD targets is superior to standard dosing in terms of reducing the time to complete clinical cure (resolution of signs and symptoms of infection, functional recovery, baseline or improved SOFA score (≤2 points), and absence of need for new antibiotics).
- Secondary objectives
- To evaluate the overall clinical efficacy of personalized dosing versus conventional dosing using variables such as: survival rate, clinical and microbiological cure rate, total length of hospital stay, number of days free of life-support therapies (vasopressors, renal replacement therapies, extracorporeal membrane oxygenation (ECMO)).
- Analyze the emergence of antimicrobial resistance in both groups.
- Compare the incidence of adverse effects (nephrotoxicity, hepatotoxicity, and neurotoxicity) between the personalized dosing group and the control group.
- Determine the percentage of patients who achieve the established PK/PD targets: ≥100% fT > MIC or ≥100% fT > 4×MIC.
- Study the influence of clinical variables (type of infection, microorganism involved, severity of clinical symptoms, etc.) on the probability of achieving PK/PD targets.
- Evaluate the relationship between the total concentration and the free fraction of the antibiotic, and its impact on achieving the desired PK/PD parameters.
- Conditions
- Bacterial Sepsis
- Being tested
- Individualized dosing of beta-lactam antibiotics based on therapeutic monitoring
- Keywords
- betalactam, therapeutic drug monitoring, sepsis, clinical cure, microbiological cure
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individualized dosing of beta-lactam antibiotics based on therapeutic monitoringOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group (individualized dosing based on therapeutic monitoring) | Experimental | Patients will receive individualized dosing of beta-lactam antibiotics based on therapeutic monitoring. Total and free plasma concentrations will be determined 48 hours after the start of antibiotic therapy and subsequently every 4-5 days, or sooner if there is a significant clinical change. Dosage adjustments will be made to achieve the defined PK/PD targets:
* Standard: ≥100% fT > MIC.
* Infections caused by multidrug-resistant pathogens, increased renal clearance, or immunosuppression: ≥100% fT > 4×MIC.
Concentrations will be interpreted in relation to the actual MIC of the identified pathogen or, failing that, to the ECOFF values defined by EUCAST. Receives: Other: Individualized dosing of beta-lactam antibiotics based on therapeutic monitoring |
| Control group (usual dosage): | No intervention | Patients will receive the usual dosage of beta-lactam antibiotics following the recommendations of clinical guidelines and hospital protocols, without individualized adjustment based on MDT. Plasma samples will also be collected, but will be stored for deferred analysis at the end of the study, with no impact on clinical management. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (9)
Time to microbiological cure (negative cultures).
Time until microbiological cultures become negative
Measured: 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
Overall survival (OS)
Length of time that patients remain alive after start of treatment.
Measured: From the start date of treatment until the end of the study, an average of 3 years.
Length of hospital stay
Number of days the patient remains hospitalized
Measured: From the date of randomization until the end of the study, an average of 3 years.
Number of days free of life support
Number of days free of life support (vasopressors, renal replacement therapy, extracorporeal membrane oxygenation).
Measured: From the date of randomization until the end of the study, an average of 3 years.
Security
Incidence of adverse effects related to beta-lactam antibiotics (nephrotoxicity, hepatotoxicity, and neurotoxicity).
Measured: From the start date of treatment until the end of the study, an average of 3 years.
Percentage of patients reaching established pharmacokinetics/pharmacodynamic (PK/PD) targets
Percentage of patients out of the total number of patients included in the study who achieve the PK/PD objective in any of the measurements taken throughout the study, with this PK/PD objective being set at 100% fT > MIC or ≥100% fT > 4×MIC, depending on clinical profile.
Measured: From the date of randomization to the date of clinical cure, assessed every 4-5 days and until the end of the study, an average of 3 years.
Ratio between total and free concentrations of beta-lactam antibiotics.
The ratio between the free beta-lactam concentration in the blood and the total concentration in each patient will be related, allowing relationships to be established between this ratio and the scope of the proposed PK/PD objective for that patient.
Measured: From the date of randomization to the date of clinical cure, assessed every 4-5 days and until the end of the study, an average of 3 years.
Identification of causative pathogens and their minimum inhibitory concentrations (MIC).
Measured: From the date of randomization until the end of the study, an average of 3 years.
Determination of the mechanism of antimicrobial resistance developed by the causative microorganism during treatment.
Measured: From the start date of treatment until the end of the study, an average of 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2025
- Study start1 Jan 2026 (estimated)
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Bacterial SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- OPTIBETA is a pragmatic, randomized, controlled, low-intervention, hospital-based clinical trial. Patients will be randomly assigned in a 1:1 ratio to one of the following groups: * Intervention: individualized dosing of beta-lactam antibiotics guided by therapeutic drug monitoring (TDM) with adjustment according to pharmacokinetic/pharmacodynamic (PK/PD) targets. * Control: standard dosing based on clinical guidelines, without individualized adjustment. The study will be open-label, although the evaluators of clinical and microbiological outcomes will be blinded to treatment assignment in order to reduce observation bias.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Complexo Hospitalario Universitario de A Coruña
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Clinico Universitario de Santiago
- Responsible party
- Principal investigator, Manuel Ángel Gómez-Ríos, Complexo Hospitalario Universitario de A Coruña
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07270523
- Sponsor's protocol ID
- OPTIBETA
- Status last verified
- Nov 2025
- First submitted
- 14 Nov 2025
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Suarez D, Ferrer R, Artigas A, Azkarate I, Garnacho-Montero J, Goma G, Levy MM, Ruiz JC; Edusepsis Study Group. Cost-effectiveness of the Surviving Sepsis Campaign protocol for severe sepsis: a prospective nation-wide study in Spain. Intensive Care Med. 2011 Mar;37(3):444-52. doi: 10.1007/s00134-010-2102-3. Epub 2010 Dec 9.
PubMed 21152895Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available.
PubMed 23984731Sakr Y, Jaschinski U, Wittebole X, Szakmany T, Lipman J, Namendys-Silva SA, Martin-Loeches I, Leone M, Lupu MN, Vincent JL; ICON Investigators. Sepsis in Intensive Care Unit Patients: Worldwide Data From the Intensive Care over Nations Audit. Open Forum Infect Dis. 2018 Nov 19;5(12):ofy313. doi: 10.1093/ofid/ofy313. eCollection 2018 Dec.
PubMed 30555852Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.
PubMed 31954465Perner A, Gordon AC, De Backer D, Dimopoulos G, Russell JA, Lipman J, Jensen JU, Myburgh J, Singer M, Bellomo R, Walsh T. Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med. 2016 Dec;42(12):1958-1969. doi: 10.1007/s00134-016-4577-z. Epub 2016 Oct 1.
PubMed 27695884Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing Sepsis as a Global Health Priority - A WHO Resolution. N Engl J Med. 2017 Aug 3;377(5):414-417. doi: 10.1056/NEJMp1707170. Epub 2017 Jun 28. No abstract available.
PubMed 28658587Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
PubMed 26903338
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Monitoring of Beta-lactams in Critically Ill Patients With Sepsis: OPTIBETA Clinical Trial Protocol
- ClinicalTrials.gov ID
- NCT07270523
- Acronym / sponsor ID
- OPTIBETA
- Conditions
- Bacterial Sepsis
- Keywords
- betalactam, therapeutic drug monitoring, sepsis, clinical cure, microbiological cure
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 198 participants (estimated)
- Lead sponsor
- Complexo Hospitalario Universitario de A CoruñaUniversity, hospital or other
- Collaborators
- Hospital Clinico Universitario de Santiago
- Study start
- 1 Jan 2026 (estimated)
- Primary completion
- 1 Sep 2028 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 8 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Sepsis is a global health problem of enormous magnitude, responsible for more than 48 million cases and 11 million deaths annually, accounting for around 20% of global mortality. Its prevalence is particularly high in critically ill patients, occurring in up to 40% of ICU admissions. In Spain, it causes more than 17,000 deaths per year, exceeding the mortality rate of some types of cancer. In addition to its clinical impact, sepsis entails a considerable economic burden, with direct costs estimated at between €20,000 and €30,000 per patient admitted to the ICU, to which must be added indirect costs arising from functional sequelae and loss of productivity. Early and appropriate antibiotic treatment is essential to improve prognosis, with beta-lactam antibiotics being the most widely used group due to their broad spectrum of action and safety profile. These drugs have time-dependent pharmacodynamics and high pharmacokinetic variability in septic patients, conditioned by factors such as multiple organ dysfunction, increased distribution volume, and renal hyperfiltration. These alterations make it difficult to achieve adequate therapeutic concentrations and can lead to both underdosing-associated with therapeutic failure and the development of resistance-and overdosing, with an increased risk of toxicity, especially neurological toxicity. These alterations make it difficult to achieve adequate therapeutic concentrations and can lead to both underdosing-associated with therapeutic failure and the development of resistance-and overdosing, with an increased risk of toxicity, especially neurological toxicity.
Therapeutic drug monitoring (TDM) applied to beta-lactam antibiotics allows for individualized dosage adjustment based on pharmacokinetic/pharmacodynamic (PK/PD) targets. Despite strong observational evidence supporting this strategy, its clinical implementation remains limited due to technical, organizational, and economic barriers, and the absence of pragmatic randomized clinical trials makes it difficult to establish its true impact on healthcare practice.
In this context, the OPTIBETA project hypothesizes that personalized dosing of beta-lactam antibiotics guided by MDT improves time to clinical cure compared to standard dosing in critically ill patients with sepsis. The primary objective of this trial is to evaluate the efficacy of individualized dosing based on MDT versus the conventional regimen in terms of reducing the time to complete clinical cure.
Hypothesis:
The administration of beta-lactam antibiotics adjusted to PK/PD targets in critically ill patients with sepsis based on plasma level determination improves clinical and microbiological cure compared to standard dosing.
Objectives:
The overall objective is to evaluate the efficacy and safety of personalized dosing of beta-lactam antibiotics based on TDM, compared to standard dosing, in critically ill patients with sepsis.
- Primary objective Evaluate whether individualized dosing of beta-lactam antibiotics based on pharmacokinetic monitoring and achievement of PK/PD targets is superior to standard dosing in terms of reducing the time to complete clinical cure (resolution of signs and symptoms of infection, functional recovery, baseline or improved SOFA score (≤2 points), and absence of need for new antibiotics).
- Secondary objectives
- To evaluate the overall clinical efficacy of personalized dosing versus conventional dosing using variables such as: survival rate, clinical and microbiological cure rate, total length of hospital stay, number of days free of life-support therapies (vasopressors, renal replacement therapies, extracorporeal membrane oxygenation (ECMO)).
- Analyze the emergence of antimicrobial resistance in both groups.
- Compare the incidence of adverse effects (nephrotoxicity, hepatotoxicity, and neurotoxicity) between the personalized dosing group and the control group.
- Determine the percentage of patients who achieve the established PK/PD targets: ≥100% fT > MIC or ≥100% fT > 4×MIC.
- Study the influence of clinical variables (type of infection, microorganism involved, severity of clinical symptoms, etc.) on the probability of achieving PK/PD targets.
- Evaluate the relationship between the total concentration and the free fraction of the antibiotic, and its impact on achieving the desired PK/PD parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- OPTIBETA is a pragmatic, randomized, controlled, low-intervention, hospital-based clinical trial. Patients will be randomly assigned in a 1:1 ratio to one of the following groups: * Intervention: individualized dosing of beta-lactam antibiotics guided by therapeutic drug monitoring (TDM) with adjustment according to pharmacokinetic/pharmacodynamic (PK/PD) targets. * Control: standard dosing based on clinical guidelines, without individualized adjustment. The study will be open-label, although the evaluators of clinical and microbiological outcomes will be blinded to treatment assignment in order to reduce observation bias.
| Arm | Type | Receives |
|---|---|---|
| Intervention group (individualized dosing based on therapeutic monitoring) | Experimental | Other: Individualized dosing of beta-lactam antibiotics based on therapeutic monitoringPatients will receive individualized dosing of beta-lactam antibiotics based on therapeutic monitoring. Total and free plasma concentrations will be determined 48 hours after the start of antibiotic therapy and subsequently every 4-5 days, or sooner if there is a significant clinical change. Dosage adjustments will be made to achieve the defined PK/PD targets: * Standard: ≥100% fT > MIC. * Infections caused by multidrug-resistant pathogens, increased renal clearance, or immunosuppression: ≥100% fT > 4×MIC. Concentrations will be interpreted in relation to the actual MIC of the identified pathogen or, failing that, to the ECOFF values defined by EUCAST. |
| Control group (usual dosage): | No intervention | –Patients will receive the usual dosage of beta-lactam antibiotics following the recommendations of clinical guidelines and hospital protocols, without individualized adjustment based on MDT. Plasma samples will also be collected, but will be stored for deferred analysis at the end of the study, with no impact on clinical management. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- Pregnancy or breastfeeding.
- Known hypersensitivity to beta-lactams.
- Discontinuation of antibiotic treatment before the first TDM determination.
- Simultaneous participation in another clinical trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Individualized dosing of beta-lactam antibiotics based on therapeutic monitoringIn 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. | Other | Intervention group (individualized dosing based on therapeutic monitoring) |
Primary outcome
Time to complete clinical cure
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.
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.
9 secondary outcomes
Time to microbiological cure (negative cultures).
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
Overall survival (OS)
Time frame: From the start date of treatment until the end of the study, an average of 3 years.
Length of hospital stay
Time frame: From the date of randomization until the end of the study, an average of 3 years.
Number of days free of life support
Time frame: From the date of randomization until the end of the study, an average of 3 years.
Security
Time frame: From the start date of treatment until the end of the study, an average of 3 years.
Percentage of patients reaching established pharmacokinetics/pharmacodynamic (PK/PD) targets
Time frame: From the date of randomization to the date of clinical cure, assessed every 4-5 days and until the end of the study, an average of 3 years.
Ratio between total and free concentrations of beta-lactam antibiotics.
Time frame: From the date of randomization to the date of clinical cure, assessed every 4-5 days and until the end of the study, an average of 3 years.
Identification of causative pathogens and their minimum inhibitory concentrations (MIC).
Time frame: From the date of randomization until the end of the study, an average of 3 years.
Determination of the mechanism of antimicrobial resistance developed by the causative microorganism during treatment.
Time frame: From the start date of treatment until the end of the study, an average of 3 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
- Background: PubMed 21152895Suarez D, Ferrer R, Artigas A, Azkarate I, Garnacho-Montero J, Goma G, Levy MM, Ruiz JC; Edusepsis Study Group. Cost-effectiveness of the Surviving Sepsis Campaign protocol for severe sepsis: a prospective nation-wide study in Spain. Intensive Care Med. 2011 Mar;37(3):444-52. doi: 10.1007/s00134-010-2102-3. Epub 2010 Dec 9.
- Background: PubMed 23984731Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available.
- Background: PubMed 30555852Sakr Y, Jaschinski U, Wittebole X, Szakmany T, Lipman J, Namendys-Silva SA, Martin-Loeches I, Leone M, Lupu MN, Vincent JL; ICON Investigators. Sepsis in Intensive Care Unit Patients: Worldwide Data From the Intensive Care over Nations Audit. Open Forum Infect Dis. 2018 Nov 19;5(12):ofy313. doi: 10.1093/ofid/ofy313. eCollection 2018 Dec.
- Background: PubMed 31954465Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.
- Background: PubMed 27695884Perner A, Gordon AC, De Backer D, Dimopoulos G, Russell JA, Lipman J, Jensen JU, Myburgh J, Singer M, Bellomo R, Walsh T. Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med. 2016 Dec;42(12):1958-1969. doi: 10.1007/s00134-016-4577-z. Epub 2016 Oct 1.
- Background: PubMed 28658587Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing Sepsis as a Global Health Priority - A WHO Resolution. N Engl J Med. 2017 Aug 3;377(5):414-417. doi: 10.1056/NEJMp1707170. Epub 2017 Jun 28. No abstract available.
- Background: PubMed 26903338Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Manuel A Gómez-Rios, Anesthesiologist contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Individualized dosing of beta-lactam antibiotics based on therapeutic monitoring in people with Bacterial Sepsis, run by Complexo Hospitalario Universitario de A Coruña at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Iria Varela Rey, Pharmacist (+34697538722, iriavarela13@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to complete clinical cure (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07270523, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.