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
Results First Received: November 14, 2012  
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
Condition: Sepsis
Interventions: Drug: Metoclopramide
Drug: Zinc
Dietary Supplement: Glutamine
Drug: Selenium
Other: saline
Other: sterile water
Other: selenium
Dietary Supplement: whey-protein

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Dates of recruitment period: April 2007 - November 2009; Location: Pediatric Intensive Care Unit (PICU)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients were stratified according to immunocompromised status prior to randomization.

Reporting Groups
  Description
Enteral Zinc, Selenium, Glutamine, and IV Metoclopramide Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.
Enteral Whey Protein, IV Saline Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.

Participant Flow:   Overall Study
    Enteral Zinc, Selenium, Glutamine, and IV Metoclopramide     Enteral Whey Protein, IV Saline  
STARTED     149     144  
COMPLETED     149     144  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Daily Nutriceutical Supplementation Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.
Whey Protein Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.
Total Total of all reporting groups

Baseline Measures
    Daily Nutriceutical Supplementation     Whey Protein     Total  
Number of Participants  
[units: participants]
  149     144     293  
Age  
[units: participants]
     
<=18 years     149     144     293  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  7.9  ± 5.6     8.4  ± 5.9     8.1  ± 5.7  
Gender  
[units: participants]
     
Female     69     79     148  
Male     80     65     145  
Region of Enrollment  
[units: participants]
     
United States     149     144     293  
Immune Compromised at Study Entry [1]
[units: Participants]
     
Immune compromised     14     11     25  
Immune Competent     135     133     268  
[1] Patients were classified as immune compromised if they had acquired immunodeficiency syndrome, cancer, transplantation, primary immune deficiency or chronic immune suppressant therapy.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Secondary:   Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days   [ Time Frame: 48 hours after PICU admission till discharge from PICU ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days
Measure Description No text entered.
Time Frame 48 hours after PICU admission till discharge from PICU  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients analyzed by intention to treat

Reporting Groups
  Description
Daily Nutriceutical Supplementation Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.
Whey Protein Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.

Measured Values
    Daily Nutriceutical Supplementation     Whey Protein  
Number of Participants Analyzed  
[units: participants]
  149     144  
Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days  
[units: Mean number of events per 100 study days]
Mean ( 95% Confidence Interval )
  4.99  
  ( 4.12 to 5.99 )  
  4.83  
  ( 4.01 to 5.77 )  


Statistical Analysis 1 for Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days
Groups [1] All groups
Method [2] Rate analysis (see comments)
P Value [3] 0.81
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis of equal event rates in the two study arms.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  95% CIs were calculated for rates in each arm, and rates compared between arms, via approach of DR Cox, Biometrika (1953), vol 40, pp. 354-60.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Antibiotic-free Days   [ Time Frame: 48 hours after admission until PICU discharge ]

4.  Secondary:   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 ]

5.  Secondary:   All-cause 28-day Mortality Rate.   [ Time Frame: 28 days after admission to the PICU ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The Data Safety Monitoring Board met on November 30, 2009. Interim analysis of the first 273 patients was presented. Per the Board's recommendations, the study was terminated based on futility.  


Results Point of Contact:  
Name/Title: Jeri Burr, MS, RN-BC, CCRC
Organization: University of Utah
phone: 801-587-7753
e-mail: jeri.burr@hsc.utah.edu


Publications of Results:
Other 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, 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