Lorazepam Sedation for Critically Ill Children

The EMMES Corporation

Status and phase: Completed; Phase 3; Phase 2

Conditions: Critical Illness

Treatments: Drug: Lorazepam; Drug: Midazolam; Drug: Lorazepam CI

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00109395

HHSN275200403367C (contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 179 patients

Sex: All

Ages: 1 day to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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179 participants in 3 patient groups

Lorazepam Intermittent bolus

Active Comparator group

Description:

lorazepam administered by intermittent bolus

Treatment:

Drug: Lorazepam

lorazepam continuous infusion

Active Comparator group

Description:

lorazepam administered by continuous infusion

Treatment:

Drug: Lorazepam CI

midazolam continous infusion

Active Comparator group

Description:

midazolam administered by continous infusion

Treatment:

Drug: Midazolam