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
  Purpose

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.


Condition Intervention Phase
Staphylococcus Aureus Bloodstream Infection
Drug: Trimethoprim-Sulfamethoxazole
Drug: Clindamycin
Drug: Linezolid
Drug: Flucloxacillin
Drug: Cloxacillin
Drug: Vancomycin
Drug: Daptomycin
Drug: Cefazolin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Early Oral Switch Therapy in Low-risk Staphylococcus Aureus Bloodstream Infection

Resource links provided by NLM:


Further study details as provided by University of Cologne:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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


Estimated Enrollment: 430
Study Start Date: November 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
Drug: Flucloxacillin Drug: Cloxacillin Drug: Vancomycin Drug: Daptomycin Drug: Cefazolin

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792804

Contacts
Contact: Achim J Kaasch, MD +4922147832100
Contact: Christian M Bernasch

Locations
Germany
Aachen Recruiting
Aachen, Germany, 52074
Principal Investigator: Sebastian Lemmen, Prof.Dr.         
Berlin Recruiting
Berlin, Germany, 12157
Principal Investigator: Keikawus Arastéh, PD Dr.         
Uniklinik Köln Recruiting
Cologne, Germany, 50935
Contact: Bernasch       christian.bernasch@uk-koeln.de   
Principal Investigator: Gerd Fätkenheuer, Prof. Dr.         
Frankfurt Recruiting
Frankfurt/Main, Germany, 60590
Principal Investigator: Christoph Stephan, PD Dr.         
Freiburg Recruiting
Freiburg, Germany, 79106
Principal Investigator: Winfried V Kern, Prof. Dr.         
Hannover Recruiting
Hannover, Germany, 30625
Principal Investigator: Tobias Welte, Prof. Dr.         
Jena Recruiting
Jena, Germany, 07743
Principal Investigator: Matthias Pletz, Prof. Dr.         
Krefeld Recruiting
Krefeld, Germany, 47805
Principal Investigator: Katrin Kösters, Dr.         
Leverkusen Recruiting
Leverkusen, Germany, 51375
Principal Investigator: Stefan Reuter, PD Dr.         
Lübeck Recruiting
Lübeck, Germany, 23562
Principal Investigator: Jan Rupp, Prof. Dr.         
Regensburg Recruiting
Regensburg, Germany, 93053
Principal Investigator: Bernd Salzberger, Prof. Dr.         
Ulm Recruiting
Ulm, Germany, 89081
Principal Investigator: Georg Härtner, Dr.         
Netherlands
Amsterdam Recruiting
Amsterdam, Netherlands, 1105 AZ
Principal Investigator: Jan T.M. van der Meer, Prof. Dr.         
Breda Recruiting
Breda, Netherlands, 4814 CK Breda
Principal Investigator: Jan Kluytmans, Prof. Dr.         
Groningen Recruiting
Groningen, Netherlands, 9700 RB
Principal Investigator: Sander van Assen, Prof. Dr.         
Tilburg Recruiting
Tilburg, Netherlands, 5022GC
Principal Investigator: Jan Kluytmans, Prof. Dr.         
Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Principal Investigator: Marc Bonten, Prof. Dr.         
Spain
Barcelona I Recruiting
Barcelona, Spain, 08036
Principal Investigator: Alex Soriano, Prof. Dr.         
Barcelona II Recruiting
Barcelona, Spain, 08035
Principal Investigator: Benito Almirante, Prof. Dr.         
Sevilla Recruiting
Sevilla, Spain, 41071
Principal Investigator: Jesus Rodríguez-Baño, Prof. Dr.         
Sevilla II Recruiting
Sevilla, Spain, 41071
Principal Investigator: José Cisneros, Prof. Dr.         
United Kingdom
Nottingham Recruiting
Nottingham, United Kingdom, NG7 24 H
Principal Investigator: David Turner, Prof. Dr.         
Sponsors and Collaborators
University of Cologne
German Research Foundation
Investigators
Study Chair: Achim J Kaasch, MD University of Cologne
  More Information

No publications provided

Responsible Party: Gerd Fätkenheuer, Prof. Dr. med., University of Cologne
ClinicalTrials.gov Identifier: NCT01792804     History of Changes
Other Study ID Numbers: Uni-Koeln-1400, 2013-000577-77
Study First Received: February 13, 2013
Last Updated: January 16, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Netherlands: Medicines Evaluation Board (MEB)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Cologne:
Staphylococcus aureus
Bloodstream infection
Oral switch

Additional relevant MeSH terms:
Infection
Communicable Diseases
Anti-Bacterial Agents
Vancomycin
Clindamycin
Clindamycin palmitate
Clindamycin phosphate
Daptomycin
Cefazolin
Cloxacillin
Floxacillin
Antibiotics, Antitubercular
Linezolid
Trimethoprim
Sulfamethoxazole
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 16, 2014