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
  Purpose

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.


Condition Intervention Phase
Sepsis
Drug: Metoclopramide
Drug: Zinc
Dietary Supplement: Glutamine
Drug: Selenium
Other: saline
Other: sterile water
Other: selenium
Dietary Supplement: whey-protein
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Critical Illness Stress-induced Immune Suppression Prevention Trial

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 293
Study Start Date: April 2007
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: zinc selenium glutamine metoclopramide
metoclopramide, zinc, selenium, and glutamine
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)
Placebo Comparator: enteral whey protein and IV saline
saline, sterile water, whey protein
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   12 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395161

Locations
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Childrens Hospital of Los Angeles
Los Angeles, California, United States, 90027
University of California Los Angeles Medical Center
Los Angeles, California, United States, 90095
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Michael Dean
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
Investigators
Principal Investigator: Joseph Carcillo, MD University of Pittsburgh
  More Information

Publications:
HG Friesen. Human prolactin. Ann Rev Coll Phys Surg Can, 11:275- 281, 1978.
LL Brunton. Agents affecting gastrointestinal water flux and motility. In Limbird LE Hardman JG, editor, Goodman and Gilman's The Pharmacological Basis of Therapeutics, pages 931-933. McGraw-Hill, New York, 9th edition, 1996.
PR Dallman. White blood cells: developmental changes in numbers. In Ruolph CD Rudolph AM, Hoffman JIE, editor, Pediatrics, page 1061. Appleton and Lange, Norwalk CT, 19th edition, 1987.
E.R. Stiehm. Immunologic disorders in infants and children. W.B. Saunders, Philadelphia, PA, 1989.
C. Fischer Walker and R. E. Black. Zinc and the risk for infectious disease. Annu Rev Nutr, 24:255-75, 2004. 0199-9885 (Print) Journal Article Review.

Responsible Party: Michael Dean, Data Coordinating Center Principal Investigator, University of Utah
ClinicalTrials.gov Identifier: NCT00395161     History of Changes
Other Study ID Numbers: U01HD049934
Study First Received: October 31, 2006
Results First Received: November 14, 2012
Last Updated: April 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
sepsis
prevention
mineral supplementation

Additional relevant MeSH terms:
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Metoclopramide
Selenium
Zinc
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Trace Elements
Micronutrients
Growth Substances
Antioxidants
Protective Agents

ClinicalTrials.gov processed this record on July 29, 2014