Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood

Intellectual Disability Clinical Trial

— RESTORE-cog  

Official title:

Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02225041
• Other study ID #: 1R01HD074757-01A1
• Secondary ID: 1R01HD074757-01A
• Status: Completed
• Start date: August 2014
• Est. completion date: December 2018

Study information

• Verified date: June 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to determine the relationships between sedative exposure during pediatric critical illness and long-term neurocognitive outcomes. We will test for drug- and dose-dependent relationships between sedative exposure and neurocognitive outcomes along the early developmental spectrum and will control for baseline and environmental factors, as well as the severity and course of illness.

Hypotheses:

1. Greater exposure to benzodiazepines and/or ketamine will be associated with lower IQ even when controlling for severity of illness, hospital course, and baseline factors. In addition, benzodiazepines and/or ketamine will negatively affect other aspects of neurocognitive function.

2. Younger children exposed to benzodiazepines and/or ketamine will have worse neurocognitive outcomes than older children with similar sedative exposure and severity of illness.

Description:

Ensuring the safety and comfort of the more than 100,000 critically ill infants and young children supported on mechanical ventilation in the US each year is integral to the practice of pediatric critical care. Humane care of these young patients requires the use of sedating medications, most commonly combinations of opioids and benzodiazepines. Unfortunately, sedative use also carries risk. Animal studies found that even transient administration of benzodiazepines and other sedatives during periods of developmental synaptogenesis caused widespread neuronal apoptosis and residual learning and memory deficits. Sedation is administered for days to weeks in >90% of acutely-ill, ventilated infants and children. Thus, a commonly used treatment in critically ill young children may itself have detrimental, age-dependent long-term effects.

An opportunity to increase the understanding of the long-term cognitive effects of sedation during critical illness in children has been provided by the cluster randomized, controlled trial of a sedation protocol, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), U01 HL086622, PI Curley, 31 sites, n=2,816. This trial determined whether the trial's sedation protocol used at intervention sites decreased the duration of mechanical ventilation and sedative exposure among children with acute respiratory failure due to a primary pulmonary process. Control sites continued usual sedation practice. We collected detailed data on doses and durations of sedative medications, in-hospital course, and post-discharge quality of life.

The purpose of RESTORE-cognition is to determine the relationships between sedative exposure during pediatric critical illness and long-term neurocognitive outcomes. We will assess multiple domains of neurocognitive function 2.5-5 years post-discharge in 500 RESTORE subjects with normal baseline cognitive function aged 2 weeks to 8 years at pediatric intensive care unit admission. In addition, we will study 310 matched, healthy siblings of RESTORE subjects to provide data on an unexposed group with similar baseline biological characteristics and environment. Our goal is to increase our understanding of the relationships between sedative exposure, critical illness, and long-term neurocognitive outcomes in infants and young children.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Months to 13 Years

Eligibility

Inclusion Criteria:

RESTORE subjects

• Age =8 years and PCPC=1 at RESTORE PICU admission

• PCPC =3 at RESTORE hospital discharge Sibling control subjects

Inclusion criteria:

• Age 4 to 17 years at time of testing

• PCPC=1

• Same biological parents as primary subject

• Lives with the primary subject

Exclusion Criteria:

RESTORE subjects

• Hospital readmission that includes MV and sedation

• History of cardiac arrest, traumatic brain injury (TBI) with loss of consciousness, genetic disorder, premature birth <32 weeks gestational age, or birth weight <2500 g Sibling control subjects

• Adopted or step siblings

• History of MV and sedation, receipt of general anesthesia, cardiac arrest, TBI with loss of consciousness, genetic disorder, premature birth <32 weeks gestational age, or birth weight <2500 gm.

Related Conditions & MeSH terms

• Critical Illness
• Disease
• Intellectual Disability
• Memory Disorders
• Perceptual Disorders

Locations

Country	Name	City	State
United States	C. S. Mott Children's Hospital of the University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins Children's Center	Baltimore	Maryland
United States	University of Maryland Hospital for Children	Baltimore	Maryland
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	The Children's Hospital at Montefiore	Bronx	New York
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Medical City Children's Hospital	Dallas	Texas
United States	Duke Children's Hospital and Health Center	Durham	North Carolina
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Children's Mercy Hospital, Kansas City	Kansas City	Missouri
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Holtz Children's Hospital	Miami	Florida
United States	Monroe Carell, Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Yale-New Haven Children's Hospital	New Haven	Connecticut
United States	Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Advocate Hope Children's Hospital	Oak Lawn	Illinois
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital for Children	Orlando	Florida
United States	Lucile Salter Packard Children's Hospital at Stanford	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Children's Hospital at University of California San Francisco Medical Center	San Francisco	California
United States	University Medical Center, The University of Arizona	Tucson	Arizona
United States	Nemours/Alfred I. duPont Hospital for Children	Wilmington	Delaware
United States	University of Massachusetts Memorial Children's Medical Center	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurocognitive function at 2.5 years post-ICU discharge, as assessed using standardized tests of attention, processing speed, learning and memory, visual-spatial skills, motor skills, language, executive function, IQ, and behavior		2.5 to 5 years post-discharge