The CRISIS Prevention Study
Condition: Sepsis
MeSH terms: Sepsis
Intervention: Metoclopramide; Zinc; Glutamine; Selenium; saline; sterile water; selenium; whey-protein
Intervention description: 0.2 mg/kg/dose IV every 12 hours; one enteral dose daily of zinc chloride (10 mg/day elemental zinc for infants < or equal to one year of age, and 20 mg/day elemental zinc for patients > 1 year of age); one enteral dose daily of glutamine 0.3 gm/kg/day; one enteral dose daily of selenium (40 μg for infants < 8 months of age, 60 μg for infants 8 to 12 months of age, 90 μg for children 1-3 years, 150 μg for children 4-8 years, 280 μg for children 9 to 13 years, and 400 μg for children > 13 years); equivalent volume of intravenous saline; equivalent volume of sterile water; equivalent volume of sterile water; one enteral dose daily of whey-protein
Intervention MeSH terms: Selenium; Metoclopramide
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 293.0
Sex: All
Minimum age: 12 Months
Maximum age: 17 Years
Healthy volunteers: No
Keywords: sepsis; prevention; mineral supplementation

Summary:

      Despite strict hand washing, sterile technique, and antibiotic-coated catheters, nosocomial
      infection and sepsis remain the leading acquired causes of morbidity and mortality in
      critically ill children. Subsequent use of antibiotics to treat nosocomial infection and
      sepsis is considered a major attributable factor in the rise of antibiotic-resistant
      organisms in this population of children. This study will use a double-blind, randomized,
      controlled trial design to test the hypothesis that daily prophylaxis with metoclopramide,
      zinc, selenium and glutamine will reduce nosocomial infection and sepsis in critically ill
      children.
    

Eligibility criteria:

        Inclusion Criteria:

        During the initial accrual period for this study, prior to the first interim analysis,
        patients will be eligible for enrollment if they:

          -  are between 12 months and less than 18 years; AND

          -  are within the first 48 hours of the PICU admission; AND

          -  have an endotracheal tube, central venous catheter (new or old, tunneled or not
             tunneled), or Foley catheter; AND

          -  are anticipated to have an indwelling arterial or central venous catheter for blood
             sampling during the first three days of study enrollment.

        After the Data Safety Monitoring Board (DSMB) conducts its first interim evaluation, after
        enrollment of approximately 200 subjects, a decision will be made by the DSMB concerning
        enrollment of subjects between 40 weeks gestational age and 12 months. If the DSMB approves
        enrollment of infants after the first interim analysis, then patients will be eligible for
        enrollment if they:

          -  are between 40 weeks gestational age and less than 18 years; AND

          -  are within the first 48 hours of the PICU admission; AND

          -  have an endotracheal tube, central venous catheter (new or old, tunneled or not
             tunneled), or Foley catheter; AND

          -  are anticipated to have an indwelling arterial or central venous catheter for blood
             sampling during the first three days of study enrollment.

        Exclusion Criteria:

        During the initial accrual period for this study, prior to the first interim analysis,
        patients will be ineligible for enrollment if ANY of the following is true or anticipated:

          -  are less than 1 year age; OR

          -  are greater than or equal to 18 years of age; OR

          -  have a known allergy to metoclopramide; OR

          -  planned removal of endotracheal tube, central venous catheter, AND Foley catheters,
             within 72 hours of study enrollment, OR

          -  suspected intestinal obstruction, OR

          -  intestinal surgery or bowel disruption, OR

          -  chronic metoclopramide therapy prior to enrollment, OR

          -  failure to enroll within 48 hours of PICU admission, OR

          -  readmission to PICU in the previous 28 days, OR

          -  previously enrolled in this study, OR

          -  lack of commitment to aggressive intensive care therapies.

        After the Data Safety Monitoring Board (DSMB) conducts its first interim evaluation, after
        enrollment of approximately 200 subjects, a decision will be made by the DSMB concerning
        enrollment of subjects between 40 weeks gestational age and 12 months. If the DSMB approves
        enrollment of infants after the first interim analysis, then patients will be ineligible
        for enrollment if ANY of the following is true or anticipated:

          -  are less than 40 weeks gestational age; OR

          -  are greater than or equal to 18 years of age; OR

          -  have a known allergy to metoclopramide; OR

          -  planned removal of endotracheal tube, central venous catheter, AND Foley catheters,
             within 72 hours of study enrollment, OR

          -  suspected intestinal obstruction