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Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood (RESTORE-cog)

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ClinicalTrials.gov Identifier: NCT02225041
Recruitment Status : Recruiting
First Posted : August 25, 2014
Last Update Posted : October 15, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Pennsylvania

Brief 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.

Condition or disease
Intellectual Disability Perceptual Disorders Memory Disorders

Detailed 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.


Study Type : Observational
Estimated Enrollment : 810 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
Study Start Date : August 2014
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory




Primary Outcome Measures :
  1. 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 [ Time Frame: 2.5 to 5 years post-discharge ]


Information from the National Library of Medicine

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Ages Eligible for Study:   30 Months to 13 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
RESTORE subjects who consented for 6-month follow-up with normal baseline cognitive function aged 2 weeks to 8 years at PICU admission. In addition, we will study matched, healthy siblings of these subjects to provide data on an unexposed group with similar baseline biological characteristics and environment. If more than one sibling meets enrollment criteria, the one closest in age will be selected.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02225041


Contacts
Contact: Martha AQ Curley, RN, PhD 215.573.9449 curley@nursing.upenn.edu

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Sponsors and Collaborators
University of Pennsylvania
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Martha AQ Curley, RN, PhD University of Pennsylvania
Principal Investigator: R. Scott Watson, MD Seattle Childrens Hospital

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02225041     History of Changes
Other Study ID Numbers: 1R01HD074757-01A1 ( U.S. NIH Grant/Contract )
1R01HD074757-01A1 ( U.S. NIH Grant/Contract )
First Posted: August 25, 2014    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018

Keywords provided by University of Pennsylvania:
intensive care
critical care
child
family
survivors

Additional relevant MeSH terms:
Disease
Critical Illness
Intellectual Disability
Memory Disorders
Perceptual Disorders
Pathologic Processes
Disease Attributes
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurodevelopmental Disorders
Mental Disorders