The CRISIS Prevention Study (CRISIS)

April 16, 2013 updated by: Michael Dean

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

293

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Hospital
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital of Los Angeles
      • Los Angeles, California, United States, 90095
        • University of California Los Angeles Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: zinc selenium glutamine metoclopramide
metoclopramide, zinc, selenium, and glutamine
Drug: Metoclopramide
0.2 mg/kg/dose IV every 12 hours
Other Names:
  • 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 Names:
  • Beneprotein

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
48 hours after admission until 5 days after discharged from the PICU

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days
Time Frame: 48 hours after PICU admission till discharge from PICU
48 hours after PICU admission till discharge from PICU
Antibiotic-free Days
Time Frame: 48 hours after admission until PICU discharge
48 hours after admission until PICU discharge
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
What is reported is the number of participants with counts qualifying as lymphopenia.
from time of PICU admission till discharge from PICU
All-cause 28-day Mortality Rate.
Time Frame: 28 days after admission to the PICU
28 days after admission to the PICU

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michael Dean

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of California, Los Angeles
University of Pittsburgh
Seattle Children's Hospital
Children's National Research Institute
Children's Hospital Los Angeles
Children's Hospital of Michigan
Arkansas Children's Hospital Research Institute
Harborview Injury Prevention and Research Center

Investigators

  • Principal Investigator: Joseph Carcillo, MD, University of Pittsburgh Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

October 31, 2006

First Submitted That Met QC Criteria

October 31, 2006

First Posted (ESTIMATE)

November 2, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

April 18, 2013

Last Update Submitted That Met QC Criteria

April 16, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U01HD049934 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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