Lorazepam Sedation for Critically Ill Children - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator:	Case Western Reserve University
Information provided by (Responsible Party):	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
Critical Illness	Drug: Lorazepam Drug: Midazolam Drug: Lorazepam CI	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized Controlled Trial Comparing Lorazepam With Midazolam for Sedation of Mechanically Ventilated Pediatric Patients

Resource links provided by NLM:

Drug Information available for: Midazolam Midazolam maleate Midazolam hydrochloride Lorazepam

U.S. FDA Resources

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

Primary Outcome Measures:

Rate of Severe Adverse Events [ Time Frame: Minimum 8 hours ] [ Designated as safety issue: Yes ]
Duration of study participation
Number of bolus doses required to achieve a comfort score of 17 ≤ 26 [ Time Frame: minimum of 8 hours ] [ Designated as safety issue: No ]
A measurement of drug efficacy
Drug dose required to maintain a target comfort score of 17 ≤ 26 [ Time Frame: Minimum of 8 hours ] [ Designated as safety issue: No ]
Measurement of efficacy

Enrollment:	179
Study Start Date:	September 2004
Study Completion Date:	September 2007
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Lorazepam Intermittent bolus 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 Other Names: Ativan Versed
Active Comparator: lorazepam continuous infusion lorazepam administered by continuous infusion	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 Other Names: Ativan Versed
Active Comparator: midazolam continous infusion midazolam administered by continous infusion	Drug: Midazolam 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

No publications provided

Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00109395 History of Changes
Other Study ID Numbers:	HHSN275200403367C (contract)
Study First Received:	April 27, 2005
Last Updated:	December 13, 2011
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

Additional relevant MeSH terms:

Critical Illness
Disease Attributes
Pathologic Processes
Midazolam
Lorazepam
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs

Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 12, 2012