Clinical Trial: Antibiotic Durations for Gram-negative Bacteremia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: The PIRATE PROJECT: a Point-of-care, Informatics-based Randomized Controlled Trial for Decreasing Over-utilization of Antibiotic ThErapy in Gram-negative Bacteremia

Brief Summary: Gram-negative bacteremia (GNB) is a frequent hospital & community-acquired infection, yet there is as yet no evidence from randomized studies on the optimal duration of antibiotic therapy. This point-of-care, multicenter randomized controlled non-inferiority trial will randomize 500 patients with GNB on day 5 of appropriate antibiotic therapy to either (1) a total of 7 days of antibiotic therapy, (2) a total of 14 days of antibiotic therapy, or (3) an individualized duration of antibiotic therapy (guided by the patient's clinical course & C-reactive protein levels). The primary outcome is the incidence of clinical failure at day 30.

Detailed Summary:

Antibiotic resistance continues to grow and is now considered to be one of the most serious global threats of the 21st century. The key driver of resistance is antibiotic overuse; long antibiotic courses select for resistance among the trillions of bacteria hosted by the human body. There is as yet no evidence from randomized studies on its optimal duration of antibiotic therapy. Traditionally, guidelines have somewhat arbitrarily recommended long courses of two weeks, even though patients with no structural complications may recover after only five days of therapy. Evidence is mounting that longer courses leave patients with multi-resistant organisms. Indeed, given rising concerns over resistance, many physicians have reduced antibiotic durations for GNB to 7 days with no apparent untoward consequences.

This point-of-care, multicenter randomized controlled non-inferiority trial will randomize 500 patients with GNB on day 5 of appropriate antibiotic therapy to either (1) a total of 7 days of antibiotic therapy, (2) a total of 14 days of antibiotic therapy, or (3) an individualized duration of antibiotic therapy (guided by the patient's clinical course & C-reactive protein levels). The primary outcome is the incidence of clinical failure at day 30. Patients will be followed through day 90; secondary outcomes will include the incidence of clinical failure on days 60 and 90, the total number of antibiotic days, the incidence of antibiotic-related adverse events (including Clostridium difficile infection), the emergence of bacterial resistance, length of hospital stay. Cost-effectiveness/health-economic analyses will also be performed.

Sponsor: University of Geneva, Switzerland

Current Primary Outcome: Incidence of clinical failure in all arms [ Time Frame: day 30 (with day 1 being the first day of microbiologically efficacious antibiotic therapy) ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Incidence of clinical failure in all arms [ Time Frame: day 60 ]

  Clinical failure is defined by the presence of at least one of the following:

  • Relapse: a recurrent bacteremia due to the same bacterium occurring from the day of treatment cessation and until day 30
  • Local suppurative complication that was not present/apparent at infection onset (e.g., renal abscess in pyelonephritis, empyema in pneumonia)
  • Distant complications of the initial infection, defined by growth of the same bacterium causing the initial bacteremia (as determined by antibiotic susceptibility profiling)
  • The restarting of Gram-negative-directed antibiotic therapy after its initial discontinuation due to clinical worsening suspected to be due to the initial infecting organism and for which there is no alternate diagnosis/pathogen suspected
  • Death due to any cause through day 30
• Incidence of clinical failure in all arms [ Time Frame: day 90 ]

  Clinical failure is defined by the presence of at least one of the following:

  • Relapse: a recurrent bacteremia due to the same bacterium occurring from the day of treatment cessation and until day 30
  • Local suppurative complication that was not present/apparent at infection onset (e.g., renal abscess in pyelonephritis, empyema in pneumonia)
  • Distant complications of the initial infection, defined by growth of the same bacterium causing the initial bacteremia (as determined by antibiotic susceptibility profiling)
  • The restarting of Gram-negative-directed antibiotic therapy after its initial discontinuation due to clinical worsening suspected to be due to the initial infecting organism and for which there is no alternate diagnosis/pathogen suspected
  • Death due to any cause through day 30
• Incidence of all-cause mortality in all arms [ Time Frame: day 90 ]
  incidence of all-cause mortality
• Incidence of Clostridium difficile infection in all arms [ Time Frame: day 90 ]
  incidence of symptomatic C. difficile infection in all arms
• Incidence of emergence of resistance to the study antibiotic in all arms [ Time Frame: day 90 ]
  The incidence of emergence of resistance in micro-organisms recovered in clinical specimens (whether colonizers or etiologic agents of the gram-negative bacteremia) in all arms

Original Secondary Outcome: Same as current

Information By: University of Geneva, Switzerland

Dates:
Date Received: March 29, 2017
Date Started: April 2017
Date Completion: October 2019
Last Updated: May 26, 2017
Last Verified: May 2017