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The CRISIS Prevention Study (CRISIS)

Primary Purpose

Sepsis

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Metoclopramide
Zinc
Glutamine
Selenium
saline
sterile water
selenium
whey-protein
Sponsored by
Michael Dean
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Sepsis focused on measuring sepsis, prevention, mineral supplementation

Eligibility Criteria

12 Months - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arkansas Children's Hospital
  • Childrens Hospital of Los Angeles
  • University of California Los Angeles Medical Center
  • Children's National Medical Center
  • Children's Hospital of Michigan
  • University of Pittsburgh Medical Center
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

zinc selenium glutamine metoclopramide

enteral whey protein and IV saline

Arm Description

metoclopramide, zinc, selenium, and glutamine

saline, sterile water, whey protein

Outcomes

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.

Secondary Outcome Measures

Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days
Antibiotic-free Days
Incidence of Prolonged Lymphopenia (Absolute Lymphocyte Count Less Than or Equal to 1,000/mm³ for > or Equal to 7 Days)
What is reported is the number of participants with counts qualifying as lymphopenia.
All-cause 28-day Mortality Rate.

Full Information

First Posted
October 31, 2006
Last Updated
April 16, 2013
Sponsor
Michael Dean
Collaborators
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 National Research Institute, University of California, Los Angeles, Harborview Injury Prevention and Research Center
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1. Study Identification

Unique Protocol Identification Number
NCT00395161
Brief Title
The CRISIS Prevention Study
Acronym
CRISIS
Official Title
The Critical Illness Stress-induced Immune Suppression Prevention Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Terminated
Why Stopped
Terminated for futility on 11/30/09 based on the recommendation of the DSMB
Study Start Date
April 2007 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Michael Dean
Collaborators
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 National Research Institute, University of California, Los Angeles, Harborview Injury Prevention and Research Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
sepsis, prevention, mineral supplementation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
293 (Actual)

8. Arms, Groups, and Interventions

Arm Title
zinc selenium glutamine metoclopramide
Arm Type
Experimental
Arm Description
metoclopramide, zinc, selenium, and glutamine
Arm Title
enteral whey protein and IV saline
Arm Type
Placebo Comparator
Arm Description
saline, sterile water, whey protein
Intervention Type
Drug
Intervention Name(s)
Metoclopramide
Other Intervention Name(s)
Reglan
Intervention Description
0.2 mg/kg/dose IV every 12 hours
Intervention Type
Drug
Intervention Name(s)
Zinc
Intervention Description
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)
Intervention Type
Dietary Supplement
Intervention Name(s)
Glutamine
Intervention Description
one enteral dose daily of glutamine 0.3 gm/kg/day
Intervention Type
Drug
Intervention Name(s)
Selenium
Intervention Description
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)
Intervention Type
Other
Intervention Name(s)
saline
Intervention Description
equivalent volume of intravenous saline
Intervention Type
Other
Intervention Name(s)
sterile water
Intervention Description
equivalent volume of sterile water
Intervention Type
Other
Intervention Name(s)
selenium
Intervention Description
equivalent volume of sterile water
Intervention Type
Dietary Supplement
Intervention Name(s)
whey-protein
Other Intervention Name(s)
Beneprotein
Intervention Description
one enteral dose daily of whey-protein
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days
Time Frame
48 hours after PICU admission till discharge from PICU
Title
Antibiotic-free Days
Time Frame
48 hours after admission until PICU discharge
Title
Incidence of Prolonged Lymphopenia (Absolute Lymphocyte Count Less Than or Equal to 1,000/mm³ for > or Equal to 7 Days)
Description
What is reported is the number of participants with counts qualifying as lymphopenia.
Time Frame
from time of PICU admission till discharge from PICU
Title
All-cause 28-day Mortality Rate.
Time Frame
28 days after admission to the PICU

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Carcillo, MD
Organizational Affiliation
University of Pittsburgh Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Childrens Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
University of California Los Angeles Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

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