The CRISIS Prevention Study

NCT00395161 | Terminated Phase 3 Results DMC

• 1 other identifier: U01HD049934
• Study Type: interventional
• Target: 293
• Locations: 1 country
• Sites: 7

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.

Conditions

Sepsis

Keywords

sepsis; prevention; mineral supplementation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• All-cause 28-day Mortality Rate.

  28 days after admission to the PICU

Study Arms (2)

zinc selenium glutamine metoclopramide

EXPERIMENTAL

metoclopramide, zinc, selenium, and glutamine

Drug: Metoclopramide; Drug: Zinc; Dietary Supplement: Glutamine; Drug: Selenium

enteral whey protein and IV saline

PLACEBO COMPARATOR

saline, sterile water, whey protein

Other: saline; Other: sterile water; Other: selenium; Dietary Supplement: whey-protein

Interventions

Metoclopramide DRUG

0.2 mg/kg/dose IV every 12 hours

Also known as: Reglan

zinc selenium glutamine metoclopramide

Zinc DRUG

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)

zinc selenium glutamine metoclopramide

Glutamine DIETARY_SUPPLEMENT

one enteral dose daily of glutamine 0.3 gm/kg/day

zinc selenium glutamine metoclopramide

selenium DRUG

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)

zinc selenium glutamine metoclopramide

saline OTHER

equivalent volume of intravenous saline

enteral whey protein and IV saline

sterile water OTHER

equivalent volume of sterile water

enteral whey protein and IV saline

whey-protein DIETARY_SUPPLEMENT

one enteral dose daily of whey-protein

Also known as: Beneprotein

enteral whey protein and IV saline

Eligibility Criteria

• Age: 12 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (7)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

University of California Los Angeles Medical Center

Los Angeles, California, 90095, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (74)

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  PMID: 22079954 RESULT

MeSH Terms

Conditions

Sepsis

Interventions

Metoclopramide; Zinc; Glutamine; Selenium; Sodium Chloride; Whey

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral; Chalcogens; Minerals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds; Milk; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Dairy Products; Food; Food and Beverages

Limitations and Caveats

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

• Title: Jeri Burr, MS, RN-BC, CCRC
• Organization: University of Utah

jeri.burr@hsc.utah.edu

801-587-7753

Study Officials

• Joseph Carcillo, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Data Coordinating Center Principal Investigator

Study Record Dates

• First Submitted: October 31, 2006
• First Posted: November 2, 2006
• Study Start: April 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: April 18, 2013
• Results First Posted: April 18, 2013

Record last verified: 2013-04

Locations

US (7)