Clinical trial NCT06726395: Comparison of Cloxacillin and Benzylpenicillin in Penicillin Susceptible S. Aureus Bacteraemia
Official title: Randomized Controlled Clinical Trial Comparing Treatment With Cloxacillin Versus Benzylpenicillin in Bacteraemia Caused by Penicillin-susceptible Staphylococcus Aureus (PSSA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
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
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2024-12-10
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Observational
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

Aged ≥18 with penicillin susceptible S. aureus bacteraemia (PSSA), and able to provide written informed consent.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Survival at 90 days without any treatment complications
timeFrame: From enrollment to 90 days after end of treatment
Secondary outcomes:
measure: Mortality at 90 days
timeFrame: From enrollment to 90 days after end of treatment
measure: Relapse 90 days after end of treatment
timeFrame: From enrollment to 90 days after end of treatment
measure: Cumulative frequency of side effects within 90 days
timeFrame: From enrollment until 90 days.
measure: Cumulative frequence of change or addition of antibiotic treatment due to sideeffects or treatment failure
timeFrame: from enrollment to end of treatment duration up to 90 days
measure: Decrease of Bacterial DNA in blood samples
timeFrame: From enrollment and first 5 days
Other outcomes:
measure: Days with intravenous antibiotics
timeFrame: From enrollment and until end of treatment
measure: Different outcome measures stratified by diagnosis
timeFrame: From enrollment and up to 90 days after end of treatment
Locations:
city: Lund
country: Sweden
facility: Skånes universitetssjukhus, Region Skåne
Study officials:
affiliation: Lund University
name: Malin Hagstrand Aldman, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: