The CRISIS Prevention Study

Sepsis Clinical Trial

— CRISIS  

Official title:

The Critical Illness Stress-induced Immune Suppression Prevention Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00395161
• Other study ID #: U01HD049934
• Status: Terminated
• Phase: Phase 3
• First received: October 31, 2006
• Last updated: April 16, 2013
• Start date: April 2007
• Est. completion date: November 2009

Study information

• Verified date: April 2013
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 293
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months to 17 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Sepsis

Intervention

Drug:
• Metoclopramide
0.2 mg/kg/dose IV every 12 hours
• 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)

Other:
• saline
equivalent volume of intravenous saline
• sterile water
equivalent volume of sterile water
• selenium
equivalent volume of sterile water

Dietary Supplement:
• whey-protein
one enteral dose daily of whey-protein

Locations

Country	Name	City	State
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Childrens Hospital of Los Angeles	Los Angeles	California
United States	University of California Los Angeles Medical Center	Los Angeles	California
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (10)

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

Country where clinical trial is conducted

United States, 

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* Note: There are 74 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.		48 hours after admission until 5 days after discharged from the PICU	Yes
Secondary	Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days		48 hours after PICU admission till discharge from PICU	Yes
Secondary	Antibiotic-free Days		48 hours after admission until PICU discharge	Yes
Secondary	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.	from time of PICU admission till discharge from PICU	Yes
Secondary	All-cause 28-day Mortality Rate.		28 days after admission to the PICU	Yes