Critical Illness
Conditions
Keywords
Lorazepam, Midazolam, Best Pharmaceuticals for Children Act, Critically ill, pediatrics, mechanical ventilation, sedation
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.
Interventions
DRUGLorazepam
Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
DRUGMidazolam
Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
DRUGLorazepam CI
Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
Sponsors
Case Western Reserve University
The Emmes Company, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Days to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Severe Adverse Events | Minimum 8 hours | Duration of study participation |
| Number of bolus doses required to achieve a comfort score of 17 ≤ 26 | minimum of 8 hours | A measurement of drug efficacy |
| Drug dose required to maintain a target comfort score of 17 ≤ 26 | Minimum of 8 hours | Measurement of efficacy |
Countries
United States
Outcome results
None listed