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Trial record 3 of 7452 for:    Anti-Infective Agents AND Antibiotics, Antitubercular AND Anti-Infective Agents

Impact of a Procalcitonin Testing and Treatment Algorithm on Antibiotic Use and Outcomes in the Pediatric Intensive Care Unit (ProPICU)

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ClinicalTrials.gov Identifier: NCT03440918
Recruitment Status : Completed
First Posted : February 21, 2018
Last Update Posted : June 17, 2019
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Sophie Katz, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE February 8, 2018
First Posted Date  ICMJE February 21, 2018
Last Update Posted Date June 17, 2019
Actual Study Start Date  ICMJE February 12, 2018
Actual Primary Completion Date May 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
Days of antibiotic therapy in the first 14 days following randomization [ Time Frame: 14 days ]
Days of antibiotic therapy a participant receives following randomization will be measured
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03440918 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2018)
  • Duration of broad-spectrum antibiotic therapy [ Time Frame: up to14 days ]
    Defined as vancomycin, daptomycin, amikacin, ceftazidime, cefepime, piperacillin/tazobactam, aztreonam, carbapenems
  • Time from randomization to first appropriate antibiotic modification [ Time Frame: up to 14 days ]
    Time from randomization to first appropriate antibitoic escalation or de-escalation based on patient's clinical status and available supporting laboratory evidence, or lack thereof, of specific type of infection
  • 30-day mortality [ Time Frame: up to 30 days ]
    All-cause mortality
  • Re-initiation of antibiotics for a bacterial infection [ Time Frame: up to 30 days ]
    Re-initiation of any antibiotic for a proven or suspected bacterial infection
  • Length of intensive care unit stay [ Time Frame: up to 14 days ]
    Hospital days spent in the intensive care unit
  • Length of overall hospital stay [ Time Frame: Until hospital discharge, an average of 7 days ]
    Hospital days admitted to the hospital
  • Ventilator days [ Time Frame: up to 14 days ]
    Days spent using invasive ventilation methods (not including supplementary oxygen via nasal cannula or Vapotherm support)
  • Antibiotic-associated complications [ Time Frame: up to 14 days ]
    Antibiotic-associated complications including rash, neutropenia, thrombocytopenia, acute kidney injury [defined as increase in serum creatinine > 0.3 mg per dL or > 1.5-fold from baseline, or urine output < 0.5 mL per kg per hour for more than six hours], hepatotoxicity [defined as > 2-fold increase in alanine aminotransferase, ALT, or conjugated bilirubin], or C. difficile infection will be recorded
  • Infection with a multi-drug resistant organism [ Time Frame: up to 30 days ]
    Identification/growth of a multi-drug resistant organism from a sterile culture site. Multi-drug resistant organisms will be defined as methicillin-resistant S. aureus, vancomycin-resistant Enterococcus, 3rd generation cephalosporin non-susceptible Enterobacteriaceae, multi-drug resistant Pseudomonas aeruginosa [resistant to aminoglycosides, cephalosporins, floroquinolones and carbepenems], carbepenem-resistant Acinetobacter, and Candida spp obtained from otherwise sterile sites [i.e. blood or urine cultures]
  • Antibiotic cost [ Time Frame: up to 14 days ]
    Cost of antibiotic course will be obtained from hospital billing data
  • Adherence to the procalcitonin-guided algorithm [ Time Frame: up to 5 days ]
    Rate of clinical provider compliance or non-compliance with adherence to suggested antibiotic escalation or de-escalation made by the antimicrobial stewardship team based on procalcitonin levels will be tracked
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of a Procalcitonin Testing and Treatment Algorithm on Antibiotic Use and Outcomes in the Pediatric Intensive Care Unit
Official Title  ICMJE Prospective, Randomized Controlled Trial to Evaluate the Impact of a Procalcitonin Testing and Treatment Algorithm on Antibiotic Use and Outcomes in the Pediatric Intensive Care Unit
Brief Summary

The timely use of antibiotics can reduce morbidity and mortality associated with bacterial infections, particularly in the intensive care unit setting (ICU). Long courses of antibiotics, however, are associated with the emergence of multi-drug resistant organisms and antibiotic-associated adverse events, such as C. difficile infections. Thus, antibiotic de-escalation is an important goal of antimicrobial stewardship programs.

Procalcitonin (PCT) has been investigated as a biomarker for critically ill adult patients with bacterial infection, particularly pneumonia and sepsis. The proposed project will evaluate whether a PCT testing and treatment algorithm, implemented through daily antimicrobial stewardship audit and feedback, can promote early and safe antibiotic de-escalation in the pediatric ICU.

Detailed Description

The timely use of effective antibiotics can markedly reduce the morbidity and mortality associated with bacterial infections, particularly in the intensive care unit (ICU). However, in this setting, much antibiotic use is empiric, and administered to patients with non-bacterial or non-infectious causes of inflammation that do not respond to antibiotics. This widespread empiric use of antibiotics drives the emergence of multi-drug resistant organisms and antibiotic-associated adverse events, such as C. difficile infections. De-escalation of broad-spectrum empiric antibiotics for ICU patients without proven bacterial infections can reduce unnecessary antibiotic use, slow the development of antibiotic resistance, and reduce complications associated with antibiotic therapy. Thus, antibiotic de-escalation is an important goal of antimicrobial stewardship programs. Specific tests and pathways to predict which patients have bacterial infections and those that would benefit from antibiotic therapy would accelerate de-escalation and greatly facilitate antimicrobial stewardship efforts.

Procalcitonin (PCT) has been investigated as a biomarker for critically ill adult patients with bacterial infection, particularly pneumonia and sepsis. Following bacteria-induced activation of monocytes and adherence of monocytes to endothelial surfaces, procalcitonin is expressed and secreted. PCT levels have been shown to rise rapidly and remain elevated during ongoing bacterial infections, and PCT levels are more specific for bacterial infections than CRP or total white blood cell count. PCT rises approximately 4 hours after bacterial exposure, peaks between 12-24 hours, and has a half-life of 24 hours once the infectious stimulus is removed.

In many adult trials investigating PCT-guided algorithms for antibiotic cessation (refer to section 3.0), a high proportion of providers (up to 50%) chose not to follow algorithm guidance for subjects randomized to the PCT-guided group. Thus, although PCT appears to be a useful guide for safe antibiotic de-escalation in the ICU, the ideal method for implementing the test and integrating it into clinical care in order to maximize its impact in the pediatric population is unclear. Notably, none of the prior trials evaluated PCT-associated outcomes in critically ill children nor integrated PCT testing into antimicrobial stewardship activities.

The investigators propose the evaluation of a PCT testing and treatment algorithm on patient outcomes in the pediatric ICU, a setting in which PCT-guided antibiotic de-escalation has not been previously studied.

The proposed project will evaluate whether a procalcitonin (PCT) testing and treatment algorithm, implemented through daily antimicrobial stewardship audit and feedback, can promote early and safe antibiotic de-escalation in the pediatric ICU. The investigators will conduct a pragmatic, prospective randomized controlled trial comparing antimicrobial use and outcomes among children admitted to the ICU who receive either: 1) Routine laboratory testing and treatment with antimicrobial stewardship review (control), or 2) PCT testing and treatment with antimicrobial stewardship review (intervention). In both arms, baseline daily review of antimicrobial management by the stewardship team will occur. In the intervention arm, the stewardship provider also will recommend PCT testing and antibiotic modifications using a PCT-based treatment algorithm. PCT levels will be measured a total of four times in the intervention arm - on enrollment, then daily through day 3 post-randomization and on day 5 post-randomization. This research is not to determine if PCT is a good test; this has already been established and evaluated as part of the FDA approval process. This pragmatic outcomes trial is evaluating if use of the PCT, implemented together with antimicrobial stewardship program oversight, improves the quality of care the investigators can provide for children at Vanderbilt Children's Hospital. The investigators hypothesize that patients in the intervention arm will have shorter duration of antibiotic therapy and similar outcomes, as compared to patients in the control arm.

Specific Aims

  1. Compare antimicrobial utilization among children in the ICU who receive standard-of-care testing plus stewardship vs. PCT-based treatment plus stewardship. The investigators will compare days of antibiotic therapy in the first 14 days following randomization between the study arms. The investigators will test the hypothesis that duration of antibiotic therapy will be 2 days shorter in the group with PCT-guided management vs. the group with standard of care testing and treatment.
  2. Compare clinical outcomes and safety among children in the ICU who receive standard-of-care testing plus stewardship vs. PCT-based treatment plus stewardship. The investigators will compare mortality, length of stay, recurrence of infection, and antibiotic-associated adverse events (rash, myelosuppression, renal impairment, hepatotoxicity, C. difficile infection) between the study arms. The investigators will test the hypothesis that outcomes and safety will be comparable between the study arms.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sepsis
  • Procalcitonin
  • Antimicrobial Stewardship
Intervention  ICMJE
  • Other: Procalcitonin-Guided Antimicrobial Stewardship
    In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
  • Other: Baseline Antimicrobial Stewardship
    Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.
Study Arms  ICMJE
  • Active Comparator: Baseline Antimicrobial Stewardship
    Baseline audit of antimicrobial orders with feedback to providers by the antimicrobial stewardship team.
    Interventions:
    • Other: Procalcitonin-Guided Antimicrobial Stewardship
    • Other: Baseline Antimicrobial Stewardship
  • Experimental: Procalcitonin-Guided Antimicrobial Stewardship
    In addition to baseline audit of antimicrobial orders, the stewardship team will additionally recommend procalcitonin (PCT) testing and treatment per algorithm. PCT will be used in conjunction with clinical status and exam, and results of radiographic and laboratory studies, to make medical decisions about antibiotic therapy.
    Intervention: Other: Procalcitonin-Guided Antimicrobial Stewardship
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 13, 2019)
271
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2018)
250
Actual Study Completion Date  ICMJE May 11, 2019
Actual Primary Completion Date May 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 years of age or younger
  • Prescribed or administered antibiotics in the hospital less than or equal to 24 hours prior to enrollment
  • Have parents or legal guardians who provide informed consent
  • Provide assent (if > 7 years of age)

Exclusion Criteria:

  • Are not prescribed antibiotics in the hospital
  • Receive intravenous antibiotics within 7 days prior to identification for study enrollment
  • Primary or secondary immune deficiency
  • History of malignancy, bone marrow transplant or solid organ transplant
  • A diagnosis of cystic fibrosis
  • Neonates < 34 weeks gestation
  • Patients receiving treatment for endocarditis, osteomyelitis, meningitis, mediastinitis or other invasive infection, for which long duration of antibiotics is needed
  • Do not provide informed consent/assent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03440918
Other Study ID Numbers  ICMJE 170778
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sophie Katz, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Ritu Banerjee, MD, PhD Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP