Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 ]

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
  Hide Other Adverse Events

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.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    Daily Nutriceutical Supplementation     Whey Protein  
Total, other (not including serious) adverse events      
# participants affected / at risk     119/148     112/139  
Blood and lymphatic system disorders      
Anemia † 1    
# participants affected / at risk     9/148 (6.08%)     10/139 (7.19%)  
# events     10     11  
Coagulopathy † 1    
# participants affected / at risk     8/148 (5.41%)     4/139 (2.88%)  
# events     8     4  
Leukocytosis † 1    
# participants affected / at risk     10/148 (6.76%)     10/139 (7.19%)  
# events     11     10  
Cardiac disorders      
Bradycardia † 1    
# participants affected / at risk     17/148 (11.49%)     14/139 (10.07%)  
# events     19     15  
Tachycardia † 1    
# participants affected / at risk     11/148 (7.43%)     20/139 (14.39%)  
# events     12     24  
Gastrointestinal disorders      
Abdominal distension † 1    
# participants affected / at risk     8/148 (5.41%)     7/139 (5.04%)  
# events     8     8  
Constipation † 1    
# participants affected / at risk     21/148 (14.19%)     15/139 (10.79%)  
# events     21     15  
Diarrhea † 1    
# participants affected / at risk     13/148 (8.78%)     10/139 (7.19%)  
# events     13     13  
Emesis † 1    
# participants affected / at risk     19/148 (12.84%)     17/139 (12.23%)  
# events     25     22  
Vomiting † 1    
# participants affected / at risk     6/148 (4.05%)     10/139 (7.19%)  
# events     7     10  
General disorders      
Fever † 1    
# participants affected / at risk     13/148 (8.78%)     13/139 (9.35%)  
# events     13     15  
Hyperthermia † 1    
# participants affected / at risk     10/148 (6.76%)     9/139 (6.47%)  
# events     12     14  
Hypothermia † 1    
# participants affected / at risk     10/148 (6.76%)     8/139 (5.76%)  
# events     19     8  
Pyrexia † 1    
# participants affected / at risk     16/148 (10.81%)     14/139 (10.07%)  
# events     22     18  
Infections and infestations      
Nosocomial infection † 1    
# participants affected / at risk     8/148 (5.41%)     10/139 (7.19%)  
# events     9     13  
Sepsis † 1    
# participants affected / at risk     8/148 (5.41%)     7/139 (5.04%)  
# events     8     11  
Investigations      
BUN increased † 1    
# participants affected / at risk     11/148 (7.43%)     8/139 (5.76%)  
# events     12     9  
Blood albumin decreased † 1    
# participants affected / at risk     4/148 (2.70%)     8/139 (5.76%)  
# events     4     8  
Blood magnesium decreased † 1    
# participants affected / at risk     15/148 (10.14%)     10/139 (7.19%)  
# events     16     11  
Blood phosphorus decreased † 1    
# participants affected / at risk     13/148 (8.78%)     13/139 (9.35%)  
# events     17     14  
Blood potassium decreased † 1    
# participants affected / at risk     11/148 (7.43%)     11/139 (7.91%)  
# events     11     13  
Blood sodium decreased † 1    
# participants affected / at risk     6/148 (4.05%)     7/139 (5.04%)  
# events     6     8  
Hematocrit decreased † 1    
# participants affected / at risk     12/148 (8.11%)     10/139 (7.19%)  
# events     13     10  
Hemoglobin decreased † 1    
# participants affected / at risk     13/148 (8.78%)     10/139 (7.19%)  
# events     14     17  
Lipase increased † 1    
# participants affected / at risk     13/148 (8.78%)     5/139 (3.60%)  
# events     14     5  
Oxygen saturation decreased † 1    
# participants affected / at risk     18/148 (12.16%)     13/139 (9.35%)  
# events     20     15  
PCO2 increased † 1    
# participants affected / at risk     3/148 (2.03%)     8/139 (5.76%)  
# events     5     11  
Platelets decreased † 1    
# participants affected / at risk     6/148 (4.05%)     7/139 (5.04%)  
# events     7     8  
Metabolism and nutrition disorders      
Acidosis † 1    
# participants affected / at risk     5/148 (3.38%)     8/139 (5.76%)  
# events     7     9  
Hyperglycemia † 1    
# participants affected / at risk     21/148 (14.19%)     19/139 (13.67%)  
# events     27     21  
Hyperkalemia † 1    
# participants affected / at risk     5/148 (3.38%)     8/139 (5.76%)  
# events     5     10  
Hypernatremia † 1    
# participants affected / at risk     11/148 (7.43%)     8/139 (5.76%)  
# events     12     11  
Hypocalcemia † 1    
# participants affected / at risk     4/148 (2.70%)     8/139 (5.76%)  
# events     5     10  
Hypokalemia † 1    
# participants affected / at risk     26/148 (17.57%)     27/139 (19.42%)  
# events     30     41  
Hypomagnesemia † 1    
# participants affected / at risk     5/148 (3.38%)     7/139 (5.04%)  
# events     6     12  
Hyponatremia † 1    
# participants affected / at risk     7/148 (4.73%)     11/139 (7.91%)  
# events     8     13  
Hypophosphatemia † 1    
# participants affected / at risk     5/148 (3.38%)     8/139 (5.76%)  
# events     5     9  
Nervous system disorders      
Seizure † 1    
# participants affected / at risk     3/148 (2.03%)     7/139 (5.04%)  
# events     4     7  
Psychiatric disorders      
Agitation † 1    
# participants affected / at risk     18/148 (12.16%)     18/139 (12.95%)  
# events     18     19  
Renal and urinary disorders      
Oliguria † 1    
# participants affected / at risk     8/148 (5.41%)     8/139 (5.76%)  
# events     9     11  
Respiratory, thoracic and mediastinal disorders      
Atelectasis † 1    
# participants affected / at risk     16/148 (10.81%)     17/139 (12.23%)  
# events     18     20  
Hypoxia † 1    
# participants affected / at risk     8/148 (5.41%)     9/139 (6.47%)  
# events     10     12  
Pleural effusion † 1    
# participants affected / at risk     8/148 (5.41%)     11/139 (7.91%)  
# events     8     16  
Respiratory distress † 1    
# participants affected / at risk     7/148 (4.73%)     13/139 (9.35%)  
# events     8     21  
Stridor † 1    
# participants affected / at risk     8/148 (5.41%)     6/139 (4.32%)  
# events     8     6  
Tachypnea † 1    
# participants affected / at risk     6/148 (4.05%)     13/139 (9.35%)  
# events     6     14  
Skin and subcutaneous tissue disorders      
Skin breakdown † 1    
# participants affected / at risk     7/148 (4.73%)     8/139 (5.76%)  
# events     11     15  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     23/148 (15.54%)     16/139 (11.51%)  
# events     24     19  
Hypotension † 1    
# participants affected / at risk     32/148 (21.62%)     32/139 (23.02%)  
# events     37     39  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 13.0



  Limitations and Caveats
  Hide 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.


  More Information