DOTS: Dalbavancin as an Option for Treatment of Staphylococcus Aureus Bacteremia
Condition: Staphylococcal Bacteraemia
MeSH terms: Bacteremia
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded,
      superiority study. The study will compare dalbavancin to standard of care antibiotic therapy
      for the completion of therapy in patients with complicated bacteremia or right-sided native
      valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline
      bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin
      or a standard of care antibiotic regimen that is based upon the identification and antibiotic
      susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin
      treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg
      on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects
      randomized to the standard of care antibiotic therapy treatment group will receive an
      antibiotic regimen considered to be standard of care based on the methicillin susceptibility
      pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks
      for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the
      Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care
      antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated
      S. aureus bacteremia in the intent-to-treat population (ITT).
    

Detailed description: 
      This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded,
      superiority study. The study will compare dalbavancin to standard of care antibiotic therapy
      for the completion of therapy in patients with complicated bacteremia or right-sided native
      valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline
      bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin
      or a standard of care antibiotic regimen that is based upon the identification and antibiotic
      susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin
      treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg
      on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects
      randomized to the standard of care antibiotic therapy treatment group will receive an
      antibiotic regimen considered to be standard of care based on the methicillin susceptibility
      pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks
      for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the
      Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care
      antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated
      S. aureus bacteremia in the intent-to-treat population (ITT). The secondary objectives are 1)
      to compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy
      at day 70 in the modified intent-to-treat population (mITT). 2) to compare the safety of
      dalbavancin with that of the standard of care treatment in the modified intent-to-treat
      population (mITT). 3) to compare each individual component of the Desirability of Outcome
      Ranking (DOOR) outcome by treatment arm, in the intent-to-treat population.
    

Intervention name(s): Cefazolin; Dalbavancin; Daptomycin; Nafcillin; Oxacillin; Vancomycin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks); A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species; Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks; Nafcillin is a semi-synthetic antibiotic related to penicillin. Nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks); Oxacillin is an antibiotic used in resistant staphylococci infections. Oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks; Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. Vancomycin (dose per local standard of care × 4-6 weeks)
Intervention MeSH terms: Vancomycin; Cefazolin; Daptomycin; Dalbavancin; Oxacillin; Nafcillin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bacteremia; Dalbavancin; DOTS; Efficacy; Safety; Staphylococcus aureus