Clinical trial NCT00109395: Lorazepam Sedation for Critically Ill Children
Official title: A Randomized Controlled Trial Comparing Lorazepam With Midazolam for Sedation of Mechanically Ventilated Pediatric Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Critical Illness
Keywords: Lorazepam
Midazolam
Best Pharmaceuticals for Children Act
Critically ill
pediatrics
mechanical ventilation
sedation
Lead sponsor: The Emmes Company, LLC
Sponsor class: INDUSTRY
Collaborators: name: Case Western Reserve University
First posted: 2005-04-28
Enrollment: 179
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Rate of Severe Adverse Events
timeFrame: Minimum 8 hours
measure: Number of bolus doses required to achieve a comfort score of 17 ≤ 26
timeFrame: minimum of 8 hours
measure: Drug dose required to maintain a target comfort score of 17 ≤ 26
timeFrame: Minimum of 8 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
Study officials:
affiliation: Case Western Reserve University
name: Jeffrey L Blumer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: