Clinical trial NCT03514446: Seven Versus Fourteen Days of Treatment in Uncomplicated Staphylococcus Aureus Bacteremia
Official title: Efficacy of Seven and Fourteen Days of Antibiotic Treatment in Uncomplicated Staphylococcus Aureus Bacteremia: A Randomized, Non-blinded, Non-inferiority Interventional Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Staphylococcus Aureus Bacteremia
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2018-05-02
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Introduction: Staphylococcus aureus bacteremia (SAB) plays an important role in long-course antibiotic therapy. Current international guidelines recommend fourteen days of intravenous antibiotic treatment for SAB in order to minimize risks of secondary deep infections and complications. However, patients with simple SAB are known to have a low risk of complications. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, adverse events and duration of hospital admission. SAB7 seeks to determine if seven days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to fourteen days of treatment.

Method: The study is designed as a randomized, non-blinded, non-inferiority interventional study. Primary measure of outcome will be failure to treatment or recurrence of SAB twelve weeks after termination of antibiotic treatment. As a measure of secondary outcome the prevalence of severe adverse effects will be evaluated, in particular secondary infection with Clostridium difficile, mortality as well as public health related costs. Patients identified with uncomplicated SAB, are randomized 1:1 in two parallel arms to seven or fourteen days of antimicrobial treatment, respectively. Endpoints will be tested with a statistical non-inferiority margin of 10%.

Conclusion: SAB 7 will determine if seven days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe, potentially modifying current treatment recommendations.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years
* Blood culture positive for Staphylococcus aureus
* Antibiotic treatment with antimicrobial activity to S. aureus administrated within 12 hours of the first positive blood culture
* Temperature \< 37,5 degrees celsius at randomization
* S. aureus negative follow-up blood culture obtained 48-96 hours after microbiological verified SAB.
* Patients written consent obtained

Exclusion Criteria:

* Persistence of S. aureus bacteremia before randomization (S. aureus positive follow-up blood culture obtained 48-96 hours of the first positive blood culture)
* Polymicrobial infection
* Antibiotic treatment whit no antimicrobial activity to S. aureus administrated more than 12 hours of the first positive blood culture
* Endocarditis or other intracardiac infection demonstrated with transthoracic or transesophageal echocardiography
* Previous history of endocarditis
* Pacemaker or other intracardiac implant
* Failure to remove a likely focus of infection, such as central venous catheter within 72 hours of the first positive blood culture.
* Prosthetics in joints and bones or vascular grafts
* Pneumonia or infection involving bone or joints
* Previously bone/join infection
* S. aureus infection within the last 90 days
* Pregnancy or breastfeeding
* Neutropenia (blood neutrophils \< 1,0 x 109/l)
* Untreated cancer
* Chemotherapy within 90 days.

Primary outcomes:
measure: 90-day survival without clinical or microbiological failure to treatment or relapse
timeFrame: up to 90 days
Secondary outcomes:
measure: Microbiologically failure to treatment
timeFrame: less than 7 days after treatment termination
measure: Microbiologically relapse
timeFrame: more than 7 days after treatment termination
measure: Clinical failure to treatment or relapse
timeFrame: Up to day 90
measure: Mortality
timeFrame: Days 14, 28, 90 and 180
measure: Severe adverse events
timeFrame: Up to 26 weeks
measure: Acute renal injury
timeFrame: Up to 26 weeks
measure: Clostridium difficile infection
timeFrame: Up to 26 weeks
measure: Multidrug-resistance organism
timeFrame: Up to 26 weeks
measure: Health-associated costs
timeFrame: Up to 26 weeks
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
state: Copenhagen
Study officials:
References:
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