Staphylococcus Aureus Bacteremia Antibiotic Treatment Options (SABATO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Cologne
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Gerd Fätkenheuer, University of Cologne
ClinicalTrials.gov Identifier:
NCT01792804
First received: February 13, 2013
Last updated: January 16, 2014
Last verified: January 2014

February 13, 2013
January 16, 2014
November 2013
December 2016   (final data collection date for primary outcome measure)
SAB-related complications [ Time Frame: 90 days ] [ Designated as safety issue: No ]
S. aureus bloodstream infection-related complications (relapsing SAB, deep-seated infection with S. aureus, or attributable mortality) within 90 days
Same as current
Complete list of historical versions of study NCT01792804 on ClinicalTrials.gov Archive Site
  • Length of hospital stay [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Length of hospital stay
  • Survival [ Time Frame: 14, 30, and 90 days ] [ Designated as safety issue: No ]
    Survival at 14, 30, and 90 days
  • Complications of intravenous therapy [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Complications of intravenous therapy, such as thrombophlebitis.
Same as current
  • Clostridium difficile associated diarrhea (CDAD) [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Clostridium difficile associated diarrhea (CDAD)
  • AEs and SAEs [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Adverse events
Same as current
 
Staphylococcus Aureus Bacteremia Antibiotic Treatment Options
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.

  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.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Staphylococcus Aureus Bloodstream Infection
  • Drug: Trimethoprim-Sulfamethoxazole
  • Drug: Clindamycin
  • Drug: Linezolid
  • Drug: Flucloxacillin
  • Drug: Cloxacillin
  • Drug: Vancomycin
  • Drug: Daptomycin
  • Drug: Cefazolin
  • 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
    Interventions:
    • Drug: Trimethoprim-Sulfamethoxazole
    • Drug: Clindamycin
    • Drug: Linezolid
  • 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
    Interventions:
    • Drug: Flucloxacillin
    • Drug: Cloxacillin
    • Drug: Vancomycin
    • Drug: Daptomycin
    • Drug: Cefazolin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
430
December 2016
December 2016   (final data collection date for primary outcome measure)

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
  • At least one negative follow-up blood culture obtained within 48-72 hours after the start of adequate therapy
  • Five to seven full days of appropriate i.v. antimicrobial therapy administered prior to randomization.

Exclusion Criteria:

  • Polymicrobial bloodstream infection
  • Recent history 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
  • Signs and symptoms of complicated SAB as judged by an ID physician, such as deep-seated focus,septic shock, prolonged bacteremia, fever on two occasions within 48h before randomization,presence of non-removable foreign body.
  • Failure to remove (within 4 days) any intravascular catheter, which is present when first positive blood culture was drawn
  • Severe liver disease
  • End-stage renal disease
  • Severe immunodeficiency (e.g. primary immunodeficiency disorders, neutropenia CD4+ T-cell count <200/µl in HIV-positive patients, high-dose steroid therapy, recent hematopoietic stem cell transplantation, solid organ transplant)
  • "Do not resuscitate"-order or life expectancy < 3 months
  • Inability to take oral drugs
  • Injection drug user
  • Expected low compliance with drug regimen
  • Participation in other interventional trials
  • Pregnant women and nursing mothers
Both
18 Years and older
No
Contact: Achim J Kaasch, MD +4922147832100
Contact: Christian M Bernasch
Germany,   Netherlands,   Spain,   United Kingdom
 
NCT01792804
Uni-Koeln-1400, 2013-000577-77
Yes
Gerd Fätkenheuer, University of Cologne
University of Cologne
German Research Foundation
Study Chair: Achim J Kaasch, MD University of Cologne
University of Cologne
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP