Lorazepam Sedation for Critically Ill Children

Condition(s) targeted: Conscious Sedation; Ventilation; Critical Illness

Intervention: Lorazepam (Drug)

Phase: Phase 2/Phase 3

Status: Suspended

Sponsored by: National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
Jeffrey L Blumer, MD, PhD, Principal Investigator, Affiliation: Case Western Reserve University

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.

Official title: A Randomized Controlled Trial Comparing Lorazepam With Midazolam for Sedation of Mechanically Ventilated Pediatric Patients

Study design: Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Efficacy of lorazepam relative to midazolam for initiation and maintenance of sedation in mechanically ventilated children

Secondary outcome:

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

Detailed description: 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.

Minimum age: N/A. Maximum age: 18 Years. Gender(s): 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

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

Starting date: September 2004
Ending date: June 2008
Last updated: February 20, 2008