Lorazepam Sedation for Critically Ill Children

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: Lorazepam
* Drug: Midazolam
* Drug: Lorazepam CI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lorazepam Intermittent bolus<br>lorazepam administered by intermittent bolus | Drug: Lorazepam<br>* Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score<br>* Other names: Ativan;|
| Active Comparator: lorazepam continuous infusion<br>lorazepam administered by continuous infusion | Drug: Lorazepam CI<br>* Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score<br>* Other names: Ativan;|
| Active Comparator: midazolam continous infusion<br>midazolam administered by continous infusion | Drug: Midazolam<br>* Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score<br>* Other names: Versed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Severe Adverse Events | Duration of study participation | Minimum 8 hours | 
| Number of bolus doses required to achieve a comfort score of 17 ≤ 26 | A measurement of drug efficacy | minimum of 8 hours | 
| Drug dose required to maintain a target comfort score of 17 ≤ 26 | Measurement of efficacy | Minimum of 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lorazepam, Midazolam, Best Pharmaceuticals for Children Act, Critically ill, pediatrics, mechanical ventilation, sedation