Staphylococcus Aureus BacteraemiaPhase 4COMeBACNCT06726395
Comparison of Cloxacillin and Benzylpenicillin in Penicillin Susceptible S. Aureus Bacteraemia
A Phase 4 study testing Penicillin G_1200mg and cloxacillin in people with Staphylococcus Aureus Bacteraemia and Staphylococcal Bacteraemia, run by Region Skane at 1 site in Sweden.
Trial summary
The goal of this study is to investigate if benzylpenicillin is a better treatment option than cloxacillin in patients with penicillin-susceptible Staphylococcus aureus bacteraemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Staphylococcus Aureus Bacteraemia, Staphylococcal Bacteraemia, Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia)
- What is being tested?
- Penicillin G_1200mg and cloxacillin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 420 participants
- Where
- 1 siteSweden
- Study dates
- 10 Mar 2025to Jul 2028
- 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
- Aged ≥18 with penicillin susceptible S. aureus bacteraemia (PSSA), and able to provide written informed consent.
Who cannot join
- allergy to penicillin,
- inability to give informed consent,
- concomitant growth of other clinically significant bacteria in blood cultures
- neutropenia
- -≥ 96h with prior antibiotics
- When the per oral follow up medication can not be flukloxacillin or penicillinV/Amoxicillin (ie prosthetic joint infection)
- Patients in terminal palliation, where death is expected within 7 days.
- Where the treating physician believes cloxacillin is not a first-line treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Lisa I Påhlman, PhD, MD contact
Sweden1 site, 1 recruiting
- Recruiting
Skånes universitetssjukhus, Region Skåne
Lund, 22467
MD, PhD, Malin Hagstrand Aldman, PhD, MD, +46768766308, malin.hagstrand-aldman@skane.se
Malin Hagstrand Aldman, PhD, MD
About this study
Official title: Randomized Controlled Clinical Trial Comparing Treatment With Cloxacillin Versus Benzylpenicillin in Bacteraemia Caused by Penicillin-susceptible Staphylococcus Aureus (PSSA)
The goal of this study is to investigate if benzylpenicillin is a better treatment option than cloxacillin in patients with penicillin-susceptible Staphylococcus aureus bacteraemia.
Read the detailed description
The overall research idea of is a RCT is to test the hypothesis that benzylpenicillin is superior to cloxacillin in the treatment of PSSA bacteraemia.
Population: Adult patients (>18 years) with PSSA bacteraemia will be eligible for enrolment in the study. Exclusion criteria are allergy to penicillin, inability to give informed consent, and concomitant growth of other clinically significant bacteria in blood cultures. We are planning a nation-wide study.
Intervention: Benzylpenicillin treatment of PSSA bacteraemia will be evaluated. As soon as S. aureus has been identified in blood cultures and the susceptibility testing indicates penicillin susceptibility (Two-three days from start of treatment), patients will be randomized to continue therapy with either cloxacillin or benzylpenicillin. The duration of treatment depends on the type of infection, and details about length of therapy and dosage will be decided by the specific patient diagnosis (i.e., endocarditis, arthritis). Repeated blood cultures and echocardiography are important in the diagnostic work-up of S. aureus bacteraemia and will be included in the study protocol. Patients will also be monitored regarding adverse events, such as liver and renal impairment, rash, diarrhoea, thrombophlebitis et c., and treatment failure, relapse, and mortality.
Control: The study drug (benzylpenicillin) will be compared to cloxacillin, which is the current drug of choice for methicillin susceptible S. aureus in Sweden. Both drugs will be used at clinically recommended doses, with appropriate adjustments for renal impairment if needed. Outcome: Primary outcome is; to be alive for 90 days without any complications. Complications are defined as having any of relapse (90 days after antibiotic finished), need of change or addition of antibiotics due to side effects or treatment failure or adverse events.
- Conditions
- Staphylococcus Aureus Bacteraemia, Staphylococcal Bacteraemia, Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia), Staphylococcus (S.) Aureus Infection
- Being tested
- Penicillin G_1200mg, cloxacillin
- Keywords
- Penicillin treatment, benzylpenicillin, cloxacillin, Penicillin susceptible S. aureus, Staphylococcus aureus bacteraemia
- Medical subject headings
- Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Penicillin G_1200mgDrug
Also called bensylpenicillin, benzylpenicillin
benzylpenicillin preferred dosing 1gx4
cloxacillinDrug
cloxacillin 2gx4
| Study group | Role | What they receive |
|---|---|---|
| Benzylpenicillin treatment | Experimental | Not described Receives: Drug: Penicillin G_1200mg |
| cloxacillin | Active comparator | Not described Receives: Drug: cloxacillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival at 90 days without any treatment complications
Complications are defined as having any of; relapse within 90 days after treatment finish, need of change or addition of antibiotics due to side effects or treatment failure or adverse events.
Measured: From enrollment to 90 days after end of treatment
Secondary outcomes (5)
Mortality at 90 days
All cause mortality within 90 days from enrollment
Measured: From enrollment to 90 days after end of treatment
Relapse 90 days after end of treatment
Relapse with positive culturing from sterile sites or high suscpition of clinical relapse
Measured: From enrollment to 90 days after end of treatment
Cumulative frequency of side effects within 90 days
all side effects registered as a cumulative frequence
Measured: From enrollment until 90 days.
Cumulative frequence of change or addition of antibiotic treatment due to sideeffects or treatment failure
Every time additional antibiotics or change in antibiotic treatment is made due to either side effects or treatment failure (according to treating doctor)
Measured: from enrollment to end of treatment duration up to 90 days
Decrease of Bacterial DNA in blood samples
Bacterial DNA tested the first 5 days during study treatment.
Measured: From enrollment and first 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2024
- Study start10 Mar 2025
- Primary completionApr 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Staphylococcus Aureus BacteraemiaStudies of the same condition, open and under way.
- More trials run by Region SkaneThe 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
- Model description
- Observational
- Masking
- None (open label)
- Enrolment
- 420 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Malin Hagstrand Aldman, Region Skane
- Investigators
- Malin Hagstrand Aldman, PhD, MD, Principal investigator, Lund University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06726395
- Sponsor's protocol ID
- 2023-506860-15-00
- Other IDs
- 2023-506860-15-00, 2023
- Acronym
- COMeBAC
- Status last verified
- Apr 2026
- First submitted
- 26 Nov 2024
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To share the IPD is not supported by the Swedish ethical comite.
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Clinical Trial Comparing Treatment With Cloxacillin Versus Benzylpenicillin in Bacteraemia Caused by Penicillin-susceptible Staphylococcus Aureus (PSSA)
- ClinicalTrials.gov ID
- NCT06726395
- Acronym / sponsor ID
- COMeBAC / 2023-506860-15-00
- Conditions
- Staphylococcus Aureus Bacteraemia, Staphylococcal Bacteraemia, Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia), Staphylococcus (S.) Aureus Infection
- Keywords
- Penicillin treatment, benzylpenicillin, cloxacillin, Penicillin susceptible S. aureus, Staphylococcus aureus bacteraemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 420 participants (estimated)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Study start
- 10 Mar 2025 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 10 Dec 2024 (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 goal of this study is to investigate if benzylpenicillin is a better treatment option than cloxacillin in patients with penicillin-susceptible Staphylococcus aureus bacteraemia.
Detailed description
The overall research idea of is a RCT is to test the hypothesis that benzylpenicillin is superior to cloxacillin in the treatment of PSSA bacteraemia.
Population: Adult patients (>18 years) with PSSA bacteraemia will be eligible for enrolment in the study. Exclusion criteria are allergy to penicillin, inability to give informed consent, and concomitant growth of other clinically significant bacteria in blood cultures. We are planning a nation-wide study.
Intervention: Benzylpenicillin treatment of PSSA bacteraemia will be evaluated. As soon as S. aureus has been identified in blood cultures and the susceptibility testing indicates penicillin susceptibility (Two-three days from start of treatment), patients will be randomized to continue therapy with either cloxacillin or benzylpenicillin. The duration of treatment depends on the type of infection, and details about length of therapy and dosage will be decided by the specific patient diagnosis (i.e., endocarditis, arthritis). Repeated blood cultures and echocardiography are important in the diagnostic work-up of S. aureus bacteraemia and will be included in the study protocol. Patients will also be monitored regarding adverse events, such as liver and renal impairment, rash, diarrhoea, thrombophlebitis et c., and treatment failure, relapse, and mortality.
Control: The study drug (benzylpenicillin) will be compared to cloxacillin, which is the current drug of choice for methicillin susceptible S. aureus in Sweden. Both drugs will be used at clinically recommended doses, with appropriate adjustments for renal impairment if needed. Outcome: Primary outcome is; to be alive for 90 days without any complications. Complications are defined as having any of relapse (90 days after antibiotic finished), need of change or addition of antibiotics due to side effects or treatment failure or adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Observational
| Arm | Type | Receives |
|---|---|---|
| Benzylpenicillin treatment | Experimental | Drug: Penicillin G_1200mg |
| cloxacillin | Active comparator | Drug: cloxacillin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Aged ≥18 with penicillin susceptible S. aureus bacteraemia (PSSA), and able to provide written informed consent.
Key exclusion criteria (8 listed)
- allergy to penicillin,
- inability to give informed consent,
- concomitant growth of other clinically significant bacteria in blood cultures
- neutropenia
- -≥ 96h with prior antibiotics
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 |
|---|---|---|
| Penicillin G_1200mgAlso: bensylpenicillin, benzylpenicillinbenzylpenicillin preferred dosing 1gx4 | Drug | Benzylpenicillin treatment |
| cloxacillincloxacillin 2gx4 | Drug | cloxacillin |
Primary outcome
Survival at 90 days without any treatment complications
Time frame: From enrollment to 90 days after end of treatment
Complications are defined as having any of; relapse within 90 days after treatment finish, need of change or addition of antibiotics due to side effects or treatment failure or adverse events.
5 secondary outcomes
Mortality at 90 days
Time frame: From enrollment to 90 days after end of treatment
Relapse 90 days after end of treatment
Time frame: From enrollment to 90 days after end of treatment
Cumulative frequency of side effects within 90 days
Time frame: From enrollment until 90 days.
Cumulative frequence of change or addition of antibiotic treatment due to sideeffects or treatment failure
Time frame: from enrollment to end of treatment duration up to 90 days
Decrease of Bacterial DNA in blood samples
Time frame: From enrollment and first 5 days
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 30 Apr 2026.
- CTISLink provided by the sponsor.
- Individual participant dataSharing planned: No. To share the IPD is not supported by the Swedish ethical comite.
Related trials for Staphylococcus Aureus Bacteraemia
RecruitingObservational study
Study of the Nasal Intracellular Reservoir of Staphylococcus Aureus in Patients With S. Aureus Bacteremia
Bacteria Infection Mechanism
RecruitingPhase 2
Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia
Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Septicemia
RecruitingPhase 4
Combination Antibiotic Therapy for Staphylococcus Aureus Bacteremia
Staphylococcus Aureus Bacteremia
RecruitingPhase 4
Dabigatran vs. Oral Anti-Xa Inhibitors in S. Aureus Bacteremia
Staphylococcus Aureus Endocarditis, Staphylococcus Aureus Septicemia
RecruitingPhase 4
Clopidogrel vs. Aspirin for Cardiovascular Risk Reduction in Patients With S. Aureus Bacteremia
Staphylococcus Aureus Endocarditis, Staphylococcus Aureus Septicemia
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.
Lisa I Påhlman, PhD, MD contact
Malin Hagstrand Aldman, PhD, MD principal investigator
Lund University
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 Penicillin G_1200mg and cloxacillin in people with Staphylococcus Aureus Bacteraemia and Staphylococcal Bacteraemia, run by Region Skane at 1 site in Sweden.
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 1 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 30 Apr 2026. 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 Sweden. 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 Malin Hagstrand Aldman, PhD (+46768766308, malin.hagstrand-aldman@skane.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival at 90 days without any treatment complications (time frame: From enrollment to 90 days after end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2026.