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
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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 ]

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
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Time Frame Adverse events were collected for 28 days.
Additional Description For adverse events, denominators reflect Safety Population of those patients receiving each treatment. Therefore, denominators are 148 patients receiving Daily Nutriceutical Supplementation and 139 patients receiving Whey Protein.

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.

Serious Adverse Events
    Daily Nutriceutical Supplementation     Whey Protein  
Total, serious adverse events      
# participants affected / at risk     73/148 (49.32%)     70/139 (50.36%)  
Cardiac disorders      
Arrhythmia † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Cardiac arrest † 1    
# participants affected / at risk     1/148 (0.68%)     4/139 (2.88%)  
# events     1     6  
Cardiopulmonary arrest † 1    
# participants affected / at risk     1/148 (0.68%)     2/139 (1.44%)  
# events     1     3  
Myocardial ischemia † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Pericardial effusion † 1    
# participants affected / at risk     1/148 (0.68%)     1/139 (0.72%)  
# events     1     1  
Congenital, familial and genetic disorders      
Sickle cell anaemia † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Endocrine disorders      
Diabetes insipidus † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Eye disorders      
Cortical blindness † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Gastrointestinal disorders      
Abdominal distension † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
GI bleed † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Gastrointestinal bleeding † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Intra-abdominal hemorrhage † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Ischemic colitis † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Pancreatitis † 1    
# participants affected / at risk     2/148 (1.35%)     1/139 (0.72%)  
# events     2     1  
Peritonitis † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
General disorders      
Brain death † 1    
# participants affected / at risk     2/148 (1.35%)     0/139 (0.00%)  
# events     2     0  
Fever † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Hyperthermia † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Multiple organ failure † 1    
# participants affected / at risk     2/148 (1.35%)     1/139 (0.72%)  
# events     2     1  
Withdrawal syndrome † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Infections and infestations      
Bacteremia † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Catheter site cellulitis † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Encephalitis viral † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Nosocomial infection † 1    
# participants affected / at risk     43/148 (29.05%)     41/139 (29.50%)  
# events     73     61  
Sepsis † 1    
# participants affected / at risk     13/148 (8.78%)     20/139 (14.39%)  
# events     14     29  
Tracheitis † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Urinary tract infection † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Injury, poisoning and procedural complications      
Brain herniation † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Subdural haematoma † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Investigations      
Amylase high † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Blood creatinine increased † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Blood culture positive † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Blood potassium decreased † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
CSF WBC increased † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Culture stool positive † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Culture urine positive † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Decreased INR † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Lipase increased † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Oxygen saturation decreased † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
PCO2 increased † 1    
# participants affected / at risk     0/148 (0.00%)     2/139 (1.44%)  
# events     0     2  
WBC increased † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Metabolism and nutrition disorders      
Hyperkalemia † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Hypoglycemia † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Hyponatremia † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Hypovolemia † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Metabolic acidosis † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Acute myeloid leukemia recurrent † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Nervous system disorders      
Cerebral edema † 1    
# participants affected / at risk     2/148 (1.35%)     1/139 (0.72%)  
# events     2     1  
Cerebral infarct † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Choreoathetoid movements † 1    
# participants affected / at risk     0/148 (0.00%)     2/139 (1.44%)  
# events     0     2  
Consciousness decreased † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Edema cerebral † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Headache † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Intracranial hemorrhage † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Intracranial pressure increased † 1    
# participants affected / at risk     2/148 (1.35%)     1/139 (0.72%)  
# events     2     1  
Ischemic stroke † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Shaking † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Psychiatric disorders      
Acute mental status changes † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Agitation † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Mental status changes † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Renal and urinary disorders      
Anuria † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Hemorrhagic cystitis † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Oliguria † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Renal failure NOS † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Respiratory, thoracic and mediastinal disorders      
ARDS † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Acute respiratory distress syndrome † 1    
# participants affected / at risk     1/148 (0.68%)     1/139 (0.72%)  
# events     1     1  
Acute respiratory failure † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Cough † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Failure respiratory † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Hypoxemia † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Hypoxia † 1    
# participants affected / at risk     1/148 (0.68%)     2/139 (1.44%)  
# events     1     2  
Paralysis of diaphragm † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Pleural effusion † 1    
# participants affected / at risk     0/148 (0.00%)     3/139 (2.16%)  
# events     0     3  
Pulmonary edema † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Pulmonary hemorrhage † 1    
# participants affected / at risk     1/148 (0.68%)     0/139 (0.00%)  
# events     1     0  
Respiratory distress † 1    
# participants affected / at risk     1/148 (0.68%)     1/139 (0.72%)  
# events     1     1  
Respiratory failure † 1    
# participants affected / at risk     4/148 (2.70%)     2/139 (1.44%)  
# events     4     2  
Stridor † 1    
# participants affected / at risk     2/148 (1.35%)     0/139 (0.00%)  
# events     2     0  
Vascular disorders      
Acute hypotension † 1    
# participants affected / at risk     0/148 (0.00%)     1/139 (0.72%)  
# events     0     1  
Hypotension † 1    
# participants affected / at risk     2/148 (1.35%)     1/139 (0.72%)  
# events     2     1  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 13.0




  Other Adverse Events


  Limitations and Caveats
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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.


  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.


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