Lorazepam Sedation for Critically Ill Children - Full Text View

Sponsors and Collaborators:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Case Western Reserve University
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00109395

Purpose

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.

Condition	Intervention	Phase
Conscious Sedation Ventilation Critical Illness	Drug: Lorazepam	Phase II Phase III

Drug Information available for: Midazolam Midazolam hydrochloride Midazolam maleate Lorazepam

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized Controlled Trial Comparing Lorazepam With Midazolam for Sedation of Mechanically Ventilated Pediatric Patients

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Efficacy of lorazepam relative to midazolam for initiation and maintenance of sedation in mechanically ventilated children [ Time Frame: during time when patient receiving sedation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Adequacy of sedation [ Time Frame: during the time patient is receiving sedation ] [ Designated as safety issue: No ]
Time to adequate sedation [ Time Frame: time from start of sedation to achievement of adequate sedation ] [ Designated as safety issue: No ]
Severe Adverse Event rate and description [ Time Frame: the duration of sedation ] [ Designated as safety issue: Yes ]
Occurrence of "critical or near critical" incidents related to inadequate sedation or analgesic agents [ Time Frame: the duration of sedation ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	340
Study Start Date:	September 2004
Estimated Study Completion Date:	June 2008
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Lorazepam Intermittent bolus: Active Comparator lorazepam administered by intermittent bolus	Drug: Lorazepam Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
lorazepam continuous infusion: Active Comparator lorazepam administered by continuous infusion	Drug: Lorazepam Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score
midazolam continous infusion: Active Comparator midazolam administered by continous infusion	Drug: Lorazepam Intravenous dosage forms, administered at dose and frequency per protocol in order to achieve adequate sedation as measured by the Comfort score

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

Ages Eligible for Study:	up to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00109395

Locations

United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106-6010

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Case Western Reserve University

Investigators

Principal Investigator:

Jeffrey L Blumer, MD, PhD

Case Western Reserve University

More Information

Responsible Party:	Case Western University ( Jeffrey Blumer, MD, PhD )
Study ID Numbers:	HHSN275200403367C (contract)
Study First Received:	April 27, 2005
Last Updated:	February 20, 2008
ClinicalTrials.gov Identifier:	NCT00109395
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Lorazepam
Midazolam
Best Pharmaceuticals for Children Act
Critically ill

pediatrics
mechanical ventilation
sedation

Study placed in the following topic categories:

Lorazepam
Critical Illness
Midazolam

Additional relevant MeSH terms:

Neurotransmitter Agents
Disease Attributes
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
Physiological Effects of Drugs
Gastrointestinal Agents
Psychotropic Drugs
Antiemetics
Central Nervous System Depressants

Pharmacologic Actions
Pathologic Processes
Autonomic Agents
Therapeutic Uses
Hypnotics and Sedatives
GABA Agents
Anti-Anxiety Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 15, 2009