The CRISIS Prevention Study

Phase 3

Terminated

Conditions: Sepsis

Interventions: Other: saline
Drug: Metoclopramide
Other: sterile water
Drug: Zinc
Dietary Supplement: Glutamine
Other: selenium
Dietary Supplement: whey-protein

Registration Number: NCT00395161

Lead Sponsor: Michael Dean

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 293

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.

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
zinc selenium glutamine metoclopramide	Glutamine	metoclopramide, zinc, selenium, and glutamine
zinc selenium glutamine metoclopramide	selenium	metoclopramide, zinc, selenium, and glutamine
enteral whey protein and IV saline	saline	saline, sterile water, whey protein
enteral whey protein and IV saline	sterile water	saline, sterile water, whey protein
enteral whey protein and IV saline	selenium	saline, sterile water, whey protein
enteral whey protein and IV saline	whey-protein	saline, sterile water, whey protein
zinc selenium glutamine metoclopramide	Metoclopramide	metoclopramide, zinc, selenium, and glutamine
zinc selenium glutamine metoclopramide	Zinc	metoclopramide, zinc, selenium, and glutamine

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days	48 hours after PICU admission till discharge from PICU
Antibiotic-free Days	48 hours after admission until PICU discharge
Incidence of Prolonged Lymphopenia (Absolute Lymphocyte Count Less Than or Equal to 1,000/mm³ for > or Equal to 7 Days)	from time of PICU admission till discharge from PICU	What is reported is the number of participants with counts qualifying as lymphopenia.
All-cause 28-day Mortality Rate.	28 days after admission to the PICU

Trial Locations

Locations (7): 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 Hospital of Michigan
🇺🇸
Detroit, Michigan, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States