Sepsis - to Reduce Mortality in the Intensive Care UnitPhase 4BULLSEYENCT06766461
Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis
A Phase 4 study testing Double dosing of beta-lactam antibiotic in people with Sepsis - to Reduce Mortality in the Intensive Care Unit and Sepsis, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
The aim of this study is to investigate if an initial short double dose of beta-lactam antibiotics will reduce mortality in critically ill patients with sepsis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis - to Reduce Mortality in the Intensive Care Unit, Sepsis, Septic Shock
- What is being tested?
- Double dosing of beta-lactam antibiotic
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 980 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 Jan 2025to 1 Dec 2027
- Phase
- Phase 4
- 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
- ≥18 years of age
- Receiving intravenous antibiotic therapy of the target drugs (including continuous infusion of beta-lactam antibiotics)
- Primary infection
- Admitted to the ICU
- Meeting the Sepsis-3 criteria for septic shock: sepsis in addition to shock requiring the start of vasopressors to maintain a mean arterial pressure 65 mmHg or greater, and a serum lac tate level greater than 2.0 mmol/L following "adequate fluid resuscitation".
Who cannot join
- Patient or legal representative not available to give informed consent within 72 hours after admittance
- Pregnancy
- Admittance for burn wounds
- Patients receiving target antibiotics only as prophylaxis within the context of Selective Diges tive tract Decontamination (SDD)
- Enrolment in another interventional trial
- Patient received the study antibiotic for more than 24 hours before inclusion
- Patient receiving extracorporeal membrane oxygenation (ECMO)
- Patient is already treated with a double dose of antibiotics based on suspected infection
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Maasstad Ziekenhuis
Rotterdam
Dr. Den Uil, 0031102913474, uilc@maasstadziekenhuis.nl
About this study
The aim of this study is to investigate if an initial short double dose of beta-lactam antibiotics will reduce mortality in critically ill patients with sepsis.
Read the detailed description
Objective
To determine if using higher dosages of beta-lactam antibiotics in the initial phase of sepsis improves clinical outcome of critically ill patients.
Main trial endpoints
The main trial endpoint is all cause 28-day mortality.
Secondary trial endpoints
Secondary trial endpoints include: Hospital length of stay, ICU length of stay, microbiological eradication, time to shock reversal, clinical cure, Δ Lactate, Δ PCT, Δ SOFA, 90- day mortality, 365-day mortality, pharmacodynamic target, post study calculation of the costs in both study, groups, EQ5D questionnaire 3 and 12 months after Admission, iMTA productivity questionnaire 3 and 12 months after admission, iMTA medical consumption questionnaire 3 and 12 months after admission and the number of adverse events.
Trial design
This is an open label, randomized controlled trial.
Trial population
The trial population will consist of adult patients admitted to the intensive care department with sepsis who will be treated according to protocol with beta-lactam antibiotics.
Interventions
During the trial participants in the intervention group will receive a double dose of antibiotics for the first 48 hours in comparison to the standard dose in the control group.
- Being tested
- Double dosing of beta-lactam antibiotic
- Keywords
- sepsis, intensive care, critically ill, antibiotic, septic shock
- Medical subject headings
- Sepsis, Shock, Septic, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Double dosing of beta-lactam antibioticDrug
This arm will receive double dosing of beta-lactam antibiotics for the first 48 hours after inclusion.
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | This arm will receive standard of care according to local protocol. |
| Intervention | Experimental | This arm will be treated with double dosages of beta-lactam antibiotics the first 48 hours after inclusion. Receives: Drug: Double dosing of beta-lactam antibiotic |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day mortality
Measured: From enrollment to 28 days
Secondary outcomes (14)
90-day mortality
Measured: From enrollment to 90 days
365-day mortality
Measured: From enrollment to the 365 days
ICU lengt of stay
Measured: From enrollment to the end of the study period at 12 months
Hospital lengt of stay
Measured: From enrollment to the end of the study period at 12 months
Time to shock reversal
From enrollment to the use of <0.1 gamma of vasopressors for 4 consecutive hours.
Measured: From enrollment to the end of the study period at 12 months
Microbiological eradication
Eradication of the causative organism from the primary source up to 30 days after therapy when confirmed by at least one repeated culture. In cases where there were no repeat cultures and the patient had resolution of the infection, microbial eradication will be presumed.
Measured: From enrollment to hospital discharge
Clinical cure
Completion of β-lactam antibiotic by day 14 without recommencement of antibiotics within 48hrs of cessation for same infective episode (investigator assessment of clinical response)
Measured: From enrollment to 14 days
Plasma concentrations of the beta-lactam antibiotics
Through concentrations take once a day for 3 consectutive days after enrollment. Target attianment is defined as 100%fT>4xMIC
Measured: From enrollment to day 3
Delta SOFA
SOFA at day 3 - SOFA at admission
Measured: From enrollment to day 3
Delta Lactate
Lactate at day 3 - lactate upon inclusion
Measured: From enrollment to day 3
Quality of life
EQ-5D-5L, a quetionnaire scoring 1 to 5 points on 5 domains. A higher score means a worse outcome.
Measured: 3 and 12 months after inclusion
Medical consumption
iMTA Medical Consumption questionnaire
Measured: 3 and 12 months after inclusion
Productivity
iMTA Productivity questionnaire
Measured: 3 and 12 months after inclusion
Adverse events and toxicity
Measured: From enrollment until the end of the study period at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2025
- Study start3 Jan 2025
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sepsis - to Reduce Mortality in the Intensive Care UnitStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 980 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maasstad Hospital, Albert Schweitzer Hospital
- Responsible party
- Principal investigator, Birgit Koch, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06766461
- Sponsor's protocol ID
- 2024-512950-13
- Other IDs
- 10140022310046, 2024-512950-13-00, U1111-1308-9223
- Acronym
- BULLSEYE
- Status last verified
- Jan 2025
- First submitted
- 27 Nov 2024
- Last updated
- 9 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Horstink MMB, Geel DR, den Uil CA, Deetman PE, Endeman H, Abdulla A, Bosch TM, Rietdijk WJR, Thielen FW, Haringman JJ, van Vliet P, Rijpstra TA, Bethlehem C, Beishuizen A, Muller AE, Koch BCP; BULLSEYE investigators. Standard versus double dosing of beta-lactam antibiotics in critically ill patients with sepsis: The BULLSEYE study protocol for a multicenter randomized controlled trial. BMC Infect Dis. 2025 Mar 21;25(1):392. doi: 10.1186/s12879-025-10747-3.
PubMed 40119275
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta-Lactam Antibiotics InitiaL ExpoSure OptimisEd in CriticallY Ill Patients with SEpsis
- ClinicalTrials.gov ID
- NCT06766461
- Acronym / sponsor ID
- BULLSEYE / 2024-512950-13
- Keywords
- sepsis, intensive care, critically ill, antibiotic, septic shock
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 980 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Maasstad Hospital, Albert Schweitzer Hospital
- Study start
- 3 Jan 2025 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 9 Jan 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.
The aim of this study is to investigate if an initial short double dose of beta-lactam antibiotics will reduce mortality in critically ill patients with sepsis.
Detailed description
Objective
To determine if using higher dosages of beta-lactam antibiotics in the initial phase of sepsis improves clinical outcome of critically ill patients.
Main trial endpoints
The main trial endpoint is all cause 28-day mortality.
Secondary trial endpoints
Secondary trial endpoints include: Hospital length of stay, ICU length of stay, microbiological eradication, time to shock reversal, clinical cure, Δ Lactate, Δ PCT, Δ SOFA, 90- day mortality, 365-day mortality, pharmacodynamic target, post study calculation of the costs in both study, groups, EQ5D questionnaire 3 and 12 months after Admission, iMTA productivity questionnaire 3 and 12 months after admission, iMTA medical consumption questionnaire 3 and 12 months after admission and the number of adverse events.
Trial design
This is an open label, randomized controlled trial.
Trial population
The trial population will consist of adult patients admitted to the intensive care department with sepsis who will be treated according to protocol with beta-lactam antibiotics.
Interventions
During the trial participants in the intervention group will receive a double dose of antibiotics for the first 48 hours in comparison to the standard dose in the control group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –This arm will receive standard of care according to local protocol. |
| Intervention | Experimental | Drug: Double dosing of beta-lactam antibioticThis arm will be treated with double dosages of beta-lactam antibiotics the first 48 hours after inclusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- ≥18 years of age
- Receiving intravenous antibiotic therapy of the target drugs (including continuous infusion of beta-lactam antibiotics)
- Primary infection
- Admitted to the ICU
- Meeting the Sepsis-3 criteria for septic shock: sepsis in addition to shock requiring the start of vasopressors to maintain a mean arterial pressure 65 mmHg or greater, and a serum lac tate level greater than 2.0 mmol/L following "adequate fluid resuscitation".
Key exclusion criteria (8 listed)
- Patient or legal representative not available to give informed consent within 72 hours after admittance
- Pregnancy
- Admittance for burn wounds
- Patients receiving target antibiotics only as prophylaxis within the context of Selective Diges tive tract Decontamination (SDD)
- Enrolment in another interventional 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 |
|---|---|---|
| Double dosing of beta-lactam antibioticThis arm will receive double dosing of beta-lactam antibiotics for the first 48 hours after inclusion. | Drug | Intervention |
Primary outcome
28-day mortality
Time frame: From enrollment to 28 days
14 secondary outcomes
90-day mortality
Time frame: From enrollment to 90 days
365-day mortality
Time frame: From enrollment to the 365 days
ICU lengt of stay
Time frame: From enrollment to the end of the study period at 12 months
Hospital lengt of stay
Time frame: From enrollment to the end of the study period at 12 months
Time to shock reversal
Time frame: From enrollment to the end of the study period at 12 months
Microbiological eradication
Time frame: From enrollment to hospital discharge
Clinical cure
Time frame: From enrollment to 14 days
Plasma concentrations of the beta-lactam antibiotics
Time frame: From enrollment to day 3
Delta SOFA
Time frame: From enrollment to day 3
Delta Lactate
Time frame: From enrollment to day 3
Quality of life
Time frame: 3 and 12 months after inclusion
Medical consumption
Time frame: 3 and 12 months after inclusion
Productivity
Time frame: 3 and 12 months after inclusion
Adverse events and toxicity
Time frame: From enrollment until the end of the study period at 12 months
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 9 Jan 2025.
- Derived from this study: PubMed 40119275Horstink MMB, Geel DR, den Uil CA, Deetman PE, Endeman H, Abdulla A, Bosch TM, Rietdijk WJR, Thielen FW, Haringman JJ, van Vliet P, Rijpstra TA, Bethlehem C, Beishuizen A, Muller AE, Koch BCP; BULLSEYE investigators. Standard versus double dosing of beta-lactam antibiotics in critically ill patients with sepsis: The BULLSEYE study protocol for a multicenter randomized controlled trial. BMC Infect Dis. 2025 Mar 21;25(1):392. doi: 10.1186/s12879-025-10747-3.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Double dosing of beta-lactam antibiotic in people with Sepsis - to Reduce Mortality in the Intensive Care Unit and Sepsis, run by Erasmus Medical Center at 1 site in Netherlands.
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 5 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 9 Jan 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 Netherlands. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Birgit C.P. Koch, PharmD (0031107033202, b.koch@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28-day mortality (time frame: From enrollment to 28 days). 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 NCT06766461, which also lists 1 linked publication.
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 9 Jan 2025.