This clinical trial is being performed under the Best Pharmaceuticals for Children Act, signed into law in 2002 in order to improve pediatric labeling for off-patent drugs. The purpose of this study is to make sure that lorazepam, when given to children who are very sick in the Intensive Care Unit and who are on a breathing machine, is safe and works as well as a drug called midazolam. Midazolam is already approved by the FDA for this use, but lorazepam is not, even though both drugs are commonly used for sedation.

Condition	Treatment or Intervention	Phase
Conscious sedation Ventilation Critical Illness	Drug: Lorazepam	Phase II Phase III

Further Study Details: 

Primary Outcomes: Efficacy of lorazepam relative to midazolam for initiation and maintenance of sedation in mechanically ventilated children
Secondary Outcomes: Adequacy of sedation; Time to adequate sedation; Severe Adverse Event rate and description; Occurrence of "critical or near critical" incidents related to inadequate sedation or analgesic agents
Expected Total Enrollment:  340

Lorazepam is used clinically for sedation of mechanically ventilated children, but has not been approved by the FDA for this indication in children. The purpose of this study, in response to the Written Request by FDA, is to determine the safety, efficacy, and dosage required for lorazepam compared with midazolam, which is approved by FDA for children for this indication. Study participants must be children who are critically ill and receiving mechanical ventilation who require sedation. Participants will be randomized to lorazepam (intermittent bolus or continuous infusion) or midazolam (continuous infusion). Sedation will be monitored using the COMFORT score. Blood will be drawn to measure lorazepam/midazolam plasma concentrations, and to measure the plasma concentrations of excipients (benzyl alcohol and glycols) in patients receiving lorazepam.

Ages Eligible for Study:  up to  18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Males or females from full term birth (at least 38 weeks post conceptual age) through 18 years
• Patients must be intubated and mechanically ventilated in the PICU less than or equal to 24 hr
• Patients in whom the use of neuromuscular blocking agents would normally NOT be expected to be used.
• Patient's parent or guardian has signed a consent form prior to initiation of study procedures
• Patients with cardiac, renal, or hepatic dysfunction will be actively sought

Exclusion Criteria:

• Life expectancy < 48 hr
• Expected duration of sedation < 48 hr
• Patient with history of hypersensitivity to any component of lorazepam, midazolam, fentanyl, thiopental
• Females pregnant or breast feeding
• Patient requires sedatives or analgesics other than study drug

Please refer to this study by ClinicalTrials.gov identifier  NCT00109395

Jeffrey L. Blumer, MD, PhD      (216) 844-3310    jeffrey.blumer@case.edu
Mary Beth Thoburn, RN, MBA      (216) 844-3681    marybeth.thoburn@uhhs.com

Ohio
      Case Western Reserve University, Cleveland,  Ohio,  44106-6010,  United States; Recruiting

Study chairs or principal investigators

Jeffrey L Blumer, MD, PhD,  Principal Investigator,  Case Western Reserve University   

Study ID Numbers:  HHSN275200403367C (contract)
Record last reviewed:  April 2005
Last Updated:  April 29, 2005
Record first received:  April 27, 2005
ClinicalTrials.gov Identifier:  NCT00109395
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-05-03