PCT Guided Stopping of Antibiotic Therapy in Children With Sepsis
Condition: Sepsis; Septic Shock; Antibiotic Use; Procalcitonin; PCT; Antimicrobial Resistance; AMR
MeSH terms: Sepsis; Toxemia
Study type: Interventional

Summary: 
      The investigators' objective is to compare the risk of treatment failure* in children
      admitted to the pediatric intensive care unit (PICU) with sepsis and managed by procalcitonin
      guided therapy for stopping of antibiotics ('PCT- guided therapy' group) with those managed
      with standard practices based on the evidence based guidelines ('control' group).

      Children with suspected or proven sepsis will be randomized to the PCT guided group or the
      standard practices group and will be followed up for the outcome measures that include
      treatment failure and mortality. The investigators plan to enroll 560 patients over a period
      of 3 years. The investigators believe that the proposed study will provide the answer to
      reducing unnecessary antibiotic usage in the PICU without causing any harm to the patient in
      the form of treatment failure and/or mortality.
    

Detailed description: 
      Sepsis and bacterial infections account for more than 50% of and intensive care (ICU)
      admissions and the mortality rates are as high as 40-60% reported in various studies.
      Although, antibiotics are crucial in deciding outcomes in children with sepsis, however, use
      of the same in non-infectious conditions has resulted in emergence of multi drug resistant
      strains with high morbidity and mortality. The number of deaths from antibiotic resistant
      bacteria is 700000 worldwide. A major driver for development of multi drug resistant bacteria
      is antibiotic use. This indiscriminate use is much more pronounced in the ICUs with
      observations from various studies indicating that 30% to 60% of antibiotics prescribed in
      ICUs are unnecessary, inappropriate, or suboptimal. This is because of two major reasons a)
      illness severity and b) difficulty in distinguishing true sepsis from other causes of SIRS.
      In order to address these problems, researchers have tried to explore the use of novel
      biomarkers to improve the accuracy, early diagnosis and stopping of antibiotic therapy of
      sepsis. One such marker that is widely studied is procalcitonin (PCT). Several studies and
      meta-analyses have demonstrated that PCT has excellent diagnostic accuracy for sepsis and has
      a potential role in de-escalating antibiotic therapy in adult patients. Unfortunately, there
      are only few observational studies and two RCT's in children published till date evaluating
      the use of PCT for diagnosis of infections or de-escalation of antibiotic therapy. Moreover,
      till date, there are no studies in critically ill children with sepsis who are faced with the
      problem of multidrug resistant infections and have the worst outcomes. Given this background,
      the investigators plan to conduct this pragmatic randomized controlled trial in children with
      sepsis admitted to the Pediatric Intensive Care Unit (PICU) and already on antibiotics. The
      investigators' objective is to compare the risk of treatment failure in children admitted to
      the PICU with sepsis and managed by PCT guided therapy for stopping of antibiotics ('study'
      group) with those managed with 'standard practices' based on the evidence based guidelines
      ('control' group). Children with suspected or proven sepsis will be randomized to the PCT
      guided group or the standard practices group and will be followed up for the outcome measures
      that include treatment failure and mortality. The investigators' would also be comparing the
      duration of antibiotic therapy between the two groups as secondary outcome measures. The
      investigators plan to enroll 560 patients over a period of 3 years. The investigators believe
      that the proposed study will provide the answer to reducing unnecessary antibiotic usage in
      the PICU without causing any harm to the patient in the form of treatment failure and/or
      mortality. The investigators also believe that in due course of time, over the years, with
      restricted antibiotic usage, the issue of multi-drug resistant microbial infections in the
      PICU will be addressed.
    

Intervention name(s): PCT group
Intervention type(s): Behavioral
Intervention description(s): In this group antibiotic therapy will be stopped based on serial PCT measurements starting from admission.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Children with suspected or proven sepsis will be randomized to the PCT guided group or the standard practices group and will be followed up for the primary outcome measure that includes treatment failure. We would also be comparing the duration of antibiotic therapy and mortality between the two groups as secondary outcome measures.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Supportive Care