7 Days Versus 14 Days of Antibiotics for Neonatal Sepsis
Condition: Infant, Newborn; Neonatal SEPSIS; Anti-bacterial Agents; Recurrence
MeSH terms: Sepsis; Toxemia; Neonatal Sepsis; Recurrence
Study type: Interventional
Phase: Phase 3

Summary: 
      The optimum duration of intravenous antibiotic therapy for culture-proven neonatal bacterial
      sepsis is not known. Current practices, ranging from 7 days to 14 days of antibiotics, are
      not evidence-based. This is a randomized, active -controlled, multi-centric, non-inferiority
      trial to compare the efficacy of a 7-day course of intravenous antibiotics versus a 14-day
      course among neonates weighing > 1000 g at birth with culture-proven bacterial sepsis that is
      uncomplicated by meningitis, bone or joint infections deep-seated abscesses. The primary
      outcome measure is a definite or probable relapse within 21 days after stoppage of
      antibiotics.
    

Detailed description: 
      The optimum duration of intravenous antibiotic therapy for uncomplicated neonatal bacterial
      septicemia is not known. Pediatricians administer anywhere between 7 to 14 days of
      antibiotics, but these practices are not evidence based. C reactive protein (CRP) guided
      antibiotic duration is based on limited data and serial quantitative CRP is both cumbersome
      and not universally available. If it could be demonstrated that a 7-day course of antibiotics
      is not inferior to a 14-day course of antibiotics in terms of relapse rates of infection,
      then a 7 day course of antibiotics could be uniformly adopted, resulting in economic savings,
      shorter duration of hospitalization, less chances of hospital acquired infections, less
      chances of antibiotic induced adverse events and less antibiotic resistance. To test this
      hypothesis, a randomized, active-controlled, multi-centric, non-inferiority trial to compare
      the efficacy of a 7-day course of intravenous antibiotics with a 14-day course has been
      planned. Subjects weighing more than 1000 g at birth with suspected sepsis will be enrolled
      and observed for a 7-day period to see if they meet eligibility criteria for randomization.
      Subjects will be randomized on the 7th day of antibiotics, if the initial blood culture grows
      a non-Staphylococcus aureus bacterial organism, if they have no meningitis, osteomyelitis,
      septic arthritis or deep seated abscess and if the sepsis goes into clinical remission by the
      5th day and remains in remission up to the 7th day of sensitive antibiotics. Subjects in the
      14-day group will receive 7 more days of antibiotics after randomization, whereas those in
      the 7-day group will receive no further antibiotics after randomization. Subjects will be
      followed up for a 35-day period after randomization. The key outcome will be treatment
      failure as measured by "definite or probable relapse" within a 21-day period after completion
      of antibiotic therapy. Secondary outcomes will include definite relapse within 21 and 28 days
      after antibiotic completion and within 28 and 35 days after randomization; and probable
      relapse at similar time points. Other secondary outcomes will include secondary infections
      and adverse events. A total sample size of 700 (350 in each arm) will be required to detect a
      non-inferiority margin of 7%, assumed event rate of 10%, with 90% power, one-sided alpha
      error of 5% and loss to follow-up of approximately 10%. Data safety monitoring board will
      monitor serious adverse events in the trial and will perform at 1/3rd and 2/3rd of expected
      recruitment. At the time of interim analysis, the DSMB will revisit the sample size of the
      study. O'Brien Fleming's stopping criteria will be used for the primary outcome while
      Pocock's stopping rule will be used for the serious adverse events.
    

Intervention name(s): 7-day course of antibiotics; 14-day course of antibiotics
Intervention type(s): Drug; Drug
Intervention description(s): Subjects in the "7-day course of antibiotics" arm of the study will receive no further antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.; Subjects in the "14-day course of antibiotics" arm of the study will receive 7 more days of antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.
Intervention MeSH terms: Anti-Bacterial Agents; Antibiotics, Antitubercular
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, outcome-assessor blinded, active-controlled, multi-centric, non-inferiority trial
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neonate; Sepsis; Antibiotics; Duration