Lorazepam Sedation for Critically Ill Children

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Lorazepam
  • Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
• Drug: Midazolam
  • Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
• Drug: Lorazepam CI
  • Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Lorazepam Intermittent bolus
  • lorazepam administered by intermittent bolus
• Active Comparator: lorazepam continuous infusion
  • lorazepam administered by continuous infusion
• Active Comparator: midazolam continous infusion
  • midazolam administered by continous infusion

Primary Measures

• Rate of Severe Adverse Events
  • Time Frame: Minimum 8 hours
    Safety Issue?: Yes
• Number of bolus doses required to achieve a comfort score of 17 ≤ 26
  • Time Frame: minimum of 8 hours
    Safety Issue?: No
• Drug dose required to maintain a target comfort score of 17 ≤ 26
  • Time Frame: Minimum of 8 hours
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) NIH

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00109395

Study ID Number: HHSN275200403367C (contract)

ClinicalTrials.gov Identifier: NCT00109395

Health Authority: United States: Food and Drug Administration