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Staphylococcus Aureus Bacteremia Antibiotic Treatment Options (SABATO)

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Heinrich-Heine University, Duesseldorf
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT01792804
First received: February 13, 2013
Last updated: March 14, 2017
Last verified: March 2017
  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 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
Intervention Model: Parallel Assignment
Masking: No masking
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 Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Length of hospital stay [ Time Frame: 90 days ]
    Length of hospital stay

  • Survival [ Time Frame: 14, 30, and 90 days ]
    Survival at 14, 30, and 90 days

  • Complications of intravenous therapy [ Time Frame: 90 days ]
    Complications of intravenous therapy, such as thrombophlebitis.


Other Outcome Measures:
  • Clostridium difficile associated diarrhea (CDAD) [ Time Frame: 90 days ]
    Clostridium difficile associated diarrhea (CDAD)

  • AEs and SAEs [ Time Frame: 90 days ]
    Adverse events


Estimated Enrollment: 430
Study Start Date: December 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (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
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

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   (Adult, Senior)
Sexes Eligible for Study:   All
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 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 follwoing:

    • 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
  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 +492118114758 achim.kaasch@hhu.de
Contact: Anna Rommerskirchen +492118112496 anna.rommerskirchen@med.uni-duesseldorf.de

Locations
France
Annecy Not yet recruiting
Annecy, France, 74000
Principal Investigator: J Gaillat, Dr         
Chambéry Not yet recruiting
Chambéry, France, 73000
Principal Investigator: E Forestier, Dr.         
Grenoble Not yet recruiting
Grenoble, France, 38700
Principal Investigator: J P Stahl, Prof. Dr.         
La Roche-sur-Yon Not yet recruiting
La Roche-sur-Yon, France, 85000
Principal Investigator: T Guimard, Dr         
Nantes Not yet recruiting
Nantes, France, 44000
Principal Investigator: D Boutoille, Prof. Dr.         
Orléans Not yet recruiting
Orléans, France, 45100
Principal Investigator: L Hocqeloux, Dr.         
Paris 5 Not yet recruiting
Paris, France, 75010
Principal Investigator: J Molina, Prof. Dr.         
Paris 1 Not yet recruiting
Paris, France, 92100
Principal Investigator: E Rouveix-Nordon, Prof. Dr.         
Paris 3 Not yet recruiting
Paris, France, 92110
Principal Investigator: B Fantin, Prof. Dr.         
Paris 2 Not yet recruiting
Paris, France, 93000
Principal Investigator: F Mechai, Dr.         
Paris 4 Not yet recruiting
Paris, France, 94010
Principal Investigator: R. Lepeule, Dr.         
Quimper Not yet recruiting
Quimper, France, 29107
Principal Investigator: J Tallarmin, Prof. Dr.         
Rennes Not yet recruiting
Rennes, France, 35000
Principal Investigator: P Tattevin, Prof. Dr.         
St. Etienne Not yet recruiting
Saint Etienne, France, 42800
Principal Investigator: F Lucht, Prof. Dr.         
Tours Not yet recruiting
Tours, France, 37000
Principal Investigator: L Bernard, Prof. Dr.         
Germany
Aachen Withdrawn
Aachen, Germany, 52074
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.         
Düsseldorf Not yet recruiting
Dusseldorf, Germany, 40225
Principal Investigator: Achim J Kaasch, 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 Withdrawn
Regensburg, Germany, 93053
Ulm Terminated
Ulm, Germany, 89081
Netherlands
Amsterdam Terminated
Amsterdam, Netherlands, 1105 AZ
Breda Recruiting
Breda, Netherlands, 4814 CK Breda
Principal Investigator: Jan Kluytmans, Prof. Dr.         
Groningen Terminated
Groningen, Netherlands, 9700 RB
Tilburg Terminated
Tilburg, Netherlands, 5022GC
Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Principal Investigator: Marc Bonten, Prof. Dr.         
Spain
Barcelona II Terminated
Barcelona, Spain, 08035
Barcelona I Recruiting
Barcelona, Spain, 08036
Principal Investigator: Alex Soriano, Prof. Dr.         
Palma Recruiting
Palma de Mallorca, Spain, 07010
Principal Investigator: Mecholr Riera, Prof. Dr.         
Sevilla II Recruiting
Sevilla, Spain, 41071
Principal Investigator: José Cisneros, Prof. Dr.         
Sevilla Recruiting
Sevilla, Spain, 41071
Principal Investigator: Jesus Rodríguez-Baño, Prof. Dr.         
United Kingdom
Nottingham Terminated
Nottingham, United Kingdom, NG7 24 H
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
German Research Foundation
Investigators
Principal Investigator: Achim J Kaasch, MD Heinrich-Heine University, Duesseldorf
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT01792804     History of Changes
Other Study ID Numbers: Uni-Koeln-1400
2013-000577-77 ( EudraCT Number )
Study First Received: February 13, 2013
Last Updated: March 14, 2017

Keywords provided by Heinrich-Heine University, Duesseldorf:
Staphylococcus aureus
Bloodstream infection
Oral switch

Additional relevant MeSH terms:
Staphylococcal Infections
Infection
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Clindamycin
Clindamycin palmitate
Clindamycin phosphate
Floxacillin
Cloxacillin
Linezolid
Cefazolin
Vancomycin
Trimethoprim, Sulfamethoxazole Drug Combination
Daptomycin
Antibiotics, Antitubercular
Trimethoprim
Sulfamethoxazole
Anti-Infective Agents
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
Cytochrome P-450 CYP2C8 Inhibitors

ClinicalTrials.gov processed this record on June 23, 2017