The CRISIS Prevention Study

This study has been terminated.
(Terminated for futility on 11/30/09 based on the recommendation of the DSMB)
Sponsor:
Collaborators:
Seattle Children's Hospital
Children's Hospital Los Angeles
Arkansas Children's Hospital Research Institute
Children's Hospital of Michigan
University of Pittsburgh
Children's Research Institute
University of California, Los Angeles
Harborview Injury Prevention and Research Center
Information provided by (Responsible Party):
Michael Dean, University of Utah
ClinicalTrials.gov Identifier:
NCT00395161
First received: October 31, 2006
Last updated: April 16, 2013
Last verified: April 2013

October 31, 2006
April 16, 2013
April 2007
November 2009   (final data collection date for primary outcome measure)
The Primary Endpoint of This Study is the Median Time Between Admission to the PICU and Occurrence of Nosocomial Infection or Clinical Sepsis in PICU Patients Who Have Endotracheal Tubes, Central Venous Catheters, or Urinary Catheters. [ Time Frame: 48 hours after admission until 5 days after discharged from the PICU ] [ Designated as safety issue: Yes ]
The primary endpoint of this study is the time (hours) between admission to the PICU and occurrence of nosocomial infection or clinical sepsis in PICU patients who have endotracheal tubes, central venous catheters, or urinary catheters.
Complete list of historical versions of study NCT00395161 on ClinicalTrials.gov Archive Site
  • Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days [ Time Frame: 48 hours after PICU admission till discharge from PICU ] [ Designated as safety issue: Yes ]
  • Antibiotic-free Days [ Time Frame: 48 hours after admission until PICU discharge ] [ Designated as safety issue: Yes ]
  • Incidence of Prolonged Lymphopenia (Absolute Lymphocyte Count Less Than or Equal to 1,000/mm³ for > or Equal to 7 Days) [ Time Frame: from time of PICU admission till discharge from PICU ] [ Designated as safety issue: Yes ]
    What is reported is the number of participants with counts qualifying as lymphopenia.
  • All-cause 28-day Mortality Rate. [ Time Frame: 28 days after admission to the PICU ] [ Designated as safety issue: Yes ]
  • Rate of nosocomial infection or clinical sepsis per 100 PICU days
  • antibiotic-free days
  • incidence of prolonged lymphopenia (absolute lymphocyte count less than or equal to 1,000/mm cubed
  • for greater than 7 days)
  • all-cause 28-day mortality rate.
Not Provided
Not Provided
 
The CRISIS Prevention Study
The Critical Illness Stress-induced Immune Suppression Prevention Trial

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.

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. Presently, "prophylaxis" strategies are used to prevent stress-induced gastrointestinal bleeding; however, no "prophylaxis" strategy is used to prevent stress-induced nosocomial infection and sepsis. When left unopposed, the stress hormone, cortisol, induces lymphocyte apoptosis, lymphopenia, and immune insufficiency. Prolactin is the counter-regulatory stress hormone that prevents cortisol-induced apoptosis and immunosuppression. Zinc, selenium, and glutamine are also important in maintenance of lymphocyte health. Critically ill patients commonly develop hypoprolactinemia secondary to increased central nervous system dopaminergic activity, as well as zinc, selenium, and glutamine deficiency caused by increased utilization and decreased supply. Hypoprolactinemia can be prevented by metoclopramide, a dopamine 2 receptor antagonist commonly used as a prokinetic in children, and zinc, selenium, and glutamine deficiency can be prevented with enteral supplementation. 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Sepsis
  • Drug: Metoclopramide
    0.2 mg/kg/dose IV every 12 hours
    Other Name: Reglan
  • Drug: Zinc
    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)
  • Dietary Supplement: Glutamine
    one enteral dose daily of glutamine 0.3 gm/kg/day
  • Drug: Selenium
    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)
  • Other: saline
    equivalent volume of intravenous saline
  • Other: sterile water
    equivalent volume of sterile water
  • Other: selenium
    equivalent volume of sterile water
  • Dietary Supplement: whey-protein
    one enteral dose daily of whey-protein
    Other Name: Beneprotein
  • Experimental: zinc selenium glutamine metoclopramide
    metoclopramide, zinc, selenium, and glutamine
    Interventions:
    • Drug: Metoclopramide
    • Drug: Zinc
    • Dietary Supplement: Glutamine
    • Drug: Selenium
  • Placebo Comparator: enteral whey protein and IV saline
    saline, sterile water, whey protein
    Interventions:
    • Other: saline
    • Other: sterile water
    • Other: selenium
    • Dietary Supplement: whey-protein

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
293
November 2009
November 2009   (final data collection date for primary outcome measure)

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
Both
12 Months to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00395161
U01HD049934
Yes
Michael Dean, University of Utah
Michael Dean
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Seattle Children's Hospital
  • Children's Hospital Los Angeles
  • Arkansas Children's Hospital Research Institute
  • Children's Hospital of Michigan
  • University of Pittsburgh
  • Children's Research Institute
  • University of California, Los Angeles
  • Harborview Injury Prevention and Research Center
Principal Investigator: Joseph Carcillo, MD University of Pittsburgh
University of Utah
April 2013

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