Staphylococcus Aureus Bacteremia Antibiotic Treatment Options (SABATO)

May 26, 2020 updated by: Heinrich-Heine University, Duesseldorf

Early Oral Switch Therapy in Low-risk Staphylococcus Aureus Bloodstream Infection

Increasing resistance to antibiotic agents has been recognized as a major health problem worldwide that will even aggravate due to the lack of new antimicrobial agents within the next decade [1]. This threat underscores the need to maximize clinical utility of existing antibiotics, through more rational prescription, e.g. optimizing duration of treatment.

Staphylococcus aureus bloodstream infection (SAB) is a common disease with about 200,000 cases occurring annually in Europe [2]. A course of at least 14 days of intravenous antimicrobials is considered standard therapy [3-5] in "uncomplicated" SAB. This relatively long course serves to prevent SAB-related complications (such as endocarditis and vertebral osteomyelitis) that may result from hematogenous dissemination to distant sites. However, there is insufficient evidence that a full course of intravenous antibiotic therapy is always required in patients with a low risk of SAB-related complications.

In a multicenter, open-label, randomized controlled trial we aim to demonstrate that an early switch from intravenous to oral antimicrobial therapy is non-inferior to a conventional 14-days course of intravenous therapy regarding efficacy and safety. An early switch from intravenous to oral therapy would provide several benefits such as earlier discharge, fewer adverse reactions associated with intravenous therapy, increased quality of life, and cost savings.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  1. WHO. WHO Global Strategy for Containment of Antimicrobial Resistance.: World Health Organization, 2001.
  2. Kern WV. Management of Staphylococcus aureus bacteremia and endocarditis: progresses and challenges. Curr Opin Infect Dis 2010;23(4):346-58.
  3. Gemmell CG, Edwards DI, Fraise AP, Gould FK, Ridgway GL, Warren RE. Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. J Antimicrob Chemother 2006;57(4):589-608.
  4. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011;52(3):e18-55.
  5. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49(1):1-45.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
215

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Annecy, France, 74000
        • Annecy
      • Chambéry, France, 73000
        • Chambery
      • Grenoble, France, 38700
        • GRENOBLE
      • La Roche-sur-Yon, France, 85000
        • La Roche-sur-Yon
      • Nantes, France, 44000
        • Nantes
      • Orléans, France, 45100
        • ORLEANS
      • Paris, France, 75010
        • Paris 5
      • Paris, France, 92100
        • Paris 1
      • Paris, France, 92110
        • Paris 3
      • Paris, France, 93000
        • Paris 2
      • Paris, France, 94010
        • Paris 4
      • Quimper, France, 29107
        • QUIMPER
      • Rennes, France, 35000
        • RENNES
      • Saint Etienne, France, 42800
        • St. Etienne
      • Tours, France, 37000
        • TOURS
  • Germany
      • Berlin, Germany, 12157
        • Berlin
      • Cologne, Germany, 50935
        • Uniklinik Köln
      • Dusseldorf, Germany, 40225
        • Düsseldorf
      • Frankfurt/Main, Germany, 60590
        • Frankfurt
      • Freiburg, Germany, 79106
        • Freiburg
      • Hannover, Germany, 30625
        • Hannover
      • Jena, Germany, 07743
        • Jena
      • Krefeld, Germany, 47805
        • Krefeld
      • Leverkusen, Germany, 51375
        • Leverkusen
      • Lübeck, Germany, 23562
        • Lübeck
      • Ulm, Germany, 89081
        • Ulm
  • Netherlands
      • Amsterdam, Netherlands, 1081
        • VUMC Amsterdam
      • Amsterdam, Netherlands, 1105 AZ
        • Amsterdam
      • Breda, Netherlands, 4814 CK Breda
        • Breda
      • Groningen, Netherlands, 9700 RB
        • Groningen
      • Groningen, Netherlands, 9700
        • UMC Groningen
      • Tilburg, Netherlands, 5022GC
        • Tilburg
      • Utrecht, Netherlands, 3584 CX
        • Utrecht
      • Utrecht, Netherlands, 5022
        • Diakonessenhuis Utrecht
  • Spain
      • Barcelona, Spain, 08035
        • Barcelona II
      • Barcelona, Spain, 08036
        • Barcelona I
      • Palma de Mallorca, Spain, 07010
        • Palma
      • Sevilla, Spain, 41071
        • Sevilla II
      • Sevilla, Spain, 41071
        • Sevilla
  • United Kingdom
      • Nottingham, United Kingdom, NG7 24 H
        • Nottingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age at least 18 years
  • Not legally incapacitated
  • Written informed consent from the trial subject has been obtained
  • Blood culture positive for S. aureus not considered to represent contamination
  • At least one negative follow-up blood culture obtained within 24-96 hours after the start of adequate antimicrobial therapy to rule out persistent bacteremia and Absence of a blood culture positive for S. aureus at the same time or thereafter.

  • Five to seven full days of appropriate i.v. antimicrobial therapy administered prior to randomization documented in the patient Chart. Appropriate therapy has all of the following characteristics:

    1. Antimicrobial therapy has to be initiated within 72h after the first positive blood culture was drawn.

    2. Provided in-vitro susceptibility and adequate dosing (as judged by the PI) preferred agents for pre-randomization antimicrobial therapy are flucloxacillin, cloxacillin, vancomycin and daptomycin. However, the following antimicrobials are allowed:

      • MSSR: penicillinase-resistant penicillins (e.g. flucloxacillin, cloxacillin), β-lactam plus β-lactamase-inhibitors (e.g. ampicillin+sulbactam, piperacillin+tazobactam), cephalosporins (except ceftazidime), carbapenems, clindamycin, fluoroquinolones, trimethoprimsulfamethoxazole, doxycycline, tigecycline, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, ceftobiprole, and macrolides.
      • MRSA: vancomycin, teicoplanin, telavancin, fluoroquinolones, clindamycin, trimethoprim-sulfamethoxazole, doxycycline, tigecycline, linezolid, daptomycin, macrolides, ceftaroline, and ceftobiprole.

Exclusion Criteria:

  • Polymicrobial bloodstream infection, defined as isolation of pathogens other than S. aureus from a blood culture obtained in the time from two days prior to the first positive blood culture with S. aureus until randomization. Common skin contaminants (coagulase-negative staphylococci, diphtheroids, Bacillus spp., and Propionibacterium spp.) detected in one of several blood cultures will not be considered to represent polymicrobial infection
  • Recent history (within 3 months) of prior S. aureus bloodstream infection
  • In vitro resistance of S. aureus to all oral or all i.v. study drugs
  • Contraindications for all oral or all i.v. study drugs
  • Previously planned Treatment with active drug against S. aureus during Intervention Phase (e.g. cotrimoxazol prophylaxis)

  • Signs and symptoms of complicated SAB as judged by an ID physician. Complicated infection is defined as at least one of the following:

    • deep-seated focus: e.g. endocarditis, pneumonia, undrained abscess, empyema, and Osteomyelitis
    • septic shock, as defined by the AACP criteria (23), within 4 days before randomization
    • prolonged bacteremia: positive follow-up blood culture more than 72h after the start of adequate antimicrobial therapy
    • body temperature >38 °C on two separate days within 48h before randomization

  • Presence of the following non-removable foreign bodies (if not removed 2 days or more before randomization):

    • prosthetic heart valve
    • deep-seated vascular graft with foreign material (e.g. PTFE or dacron graft). Hemodialysis shunts are not considered deep-seated vascular grafts.
    • ventriculo-atrial shunt

  • Presence of a prosthetic joint (if not removed 2 days or more before randomization). This is not an exclusion criterion, if all of the following conditions are fulfilled:

    • prosthetic joint was implanted at least 6 months prior, and
    • catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and
    • joint infection unlikely (no clinical or imaging signs)

  • Presence of a pacemaker or an automated implantable cardioverter Defibrillator (AICD) device (if not removed 2 days or more before randomization). This is not an exclusion criterion, if all of the following conditions are fulfilled:

    • pacemaker or AICD was implanted at least 6 months prior, and
    • catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and
    • no clinical signs of infective endocarditis, and
    • infective endocarditis unlikely by echocardiography (preferably TEE), and
    • pocket infection unlikely (no clinical or imaging signs)
  • Failure to remove any intravascular catheter which was present when first positive blood culture was drawn within 4 days of the first positive blood culture

  • Severe liver disease. This is not an exclusion criterion, if the following condition is fulfilled:

    - catheter-related infection, skin and soft tissue infection, or surgical wound infection is present

  • End-stage renal disease. This is not an exclusion criterion, if all of the following conditions are fulfilled:

    • catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and
    • no clinical signs of infective endocarditis, and
    • infective endocarditis unlikely by echocardiography (preferably TEE), and
    • in patients with a hemodialysis shunt with a non-removable foreign body (e.g. synthetic PTFE loop): no clinical signs of a shunt infection

  • Severe immunodeficiency

    • primary immunodeficiency disorders
    • neutropenia (<500 neutrophils/μl) at randomization or neutropenia expected during intervention phase due to immunosuppressive treatment
    • uncontrolled disease in HIV-positive patients
    • high-dose steroid therapy (>1 mg/kg prednisone or equivalent doses given for >4 weeks or planned during intervention)
    • immunosuppressive combination therapy with two or more drugs with different mode of action
    • hematopoietic stem cell transplantation within the past 6 months or planned during treatment period
    • solid organ transplant
    • treatment with biologicals within the previous year
  • Life expectancy < 3 months
  • Inability to take oral drugs
  • Injection drug user
  • Expected low compliance with drug regimen
  • Participation in other interventional trials within the previous three months or ongoing
  • Pregnant women and nursing mothers

  • For premenopausal women: Failure to use highly-effective contraceptive methods for 1 month after receiving study drug. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective:

    • oral hormonal contraception ('pill')
    • dermal hormonal contraception
    • vaginal hormonal contraception (NuvaRing®)
    • contraceptive plaster
    • long-acting injectable contraceptives
    • implants that release progesterone (Implanon®)
    • tubal ligation (female sterilisation)
    • intrauterine devices that release hormones (hormone spiral)
    • double barrier methods
  • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
  • Persons held in an institution by legal or official order

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Orally administered antibiotic
First choice (MRSA and MSSA): trimethoprim-sulfamethoxazole, or Second choice (MSSA): clindamycin, or Second choice (MRSA): linezolid administered for 7-9 days
Drug: Trimethoprim-Sulfamethoxazole
study drug 1
Drug: Clindamycin
study drug 2
Drug: Linezolid
study drug 3
Experimental: Intravenously administered antibiotic
First choice (MSSA): flucloxacillin [Spain: cloxacillin], or cefazolin or Second choice (MSSA): vancomycin, or First choice (MRSA): vancomycin, or Second choice (MRSA): daptomycin administered for 7-9 days
Drug: Flucloxacillin
study drug 4
Drug: Cloxacillin
study drug 5
Drug: Vancomycin
study drug 6
Drug: Daptomycin
study drug 7
Drug: Cefazolin
study drug 8

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
SAB-related complications
Time Frame: 90 days
S. aureus bloodstream infection-related complications (relapsing SAB, deep-seated infection with S. aureus, or attributable mortality) within 90 days
90 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Length of hospital stay
Time Frame: 90 days
Length of hospital stay
90 days
Survival
Time Frame: 14, 30, and 90 days
Survival at 14, 30, and 90 days
14, 30, and 90 days
Complications of intravenous therapy
Time Frame: 90 days
Complications of intravenous therapy, such as thrombophlebitis.
90 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clostridium difficile associated diarrhea (CDAD)
Time Frame: 90 days
Clostridium difficile associated diarrhea (CDAD)
90 days
AEs and SAEs
Time Frame: 90 days
Adverse events
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Heinrich-Heine University, Duesseldorf

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
German Research Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Achim J Kaasch, MD, Heinrich-Heine University, Duesseldorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 26, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 26, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 13, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 15, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Uni-Koeln-1400
  • 2013-000577-77 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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