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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02225041
Recruitment Status : Completed
First Posted : August 25, 2014
Last Update Posted : June 18, 2019
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

Tracking Information
First Submitted Date July 25, 2014
First Posted Date August 25, 2014
Last Update Posted Date June 18, 2019
Actual Study Start Date August 2014
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 21, 2014)
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 ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
Official Title Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
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.
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
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.
Condition
  • Intellectual Disability
  • Perceptual Disorders
  • Memory Disorders
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Curley MAQ, Watson RS, Cassidy AM, Burns C, Delinger RL, Angus DC, Asaro LA, Wypij D, Beers SR; RESTORE-cognition Study Investigators. Design and rationale of the "Sedation strategy and cognitive outcome after critical illness in early childhood" study. Contemp Clin Trials. 2018 Sep;72:8-15. doi: 10.1016/j.cct.2018.07.004. Epub 2018 Jul 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: June 17, 2019)
360
Original Estimated Enrollment
 (submitted: August 21, 2014)
810
Actual Study Completion Date December 2018
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 30 Months to 13 Years   (Child)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02225041
Other Study ID Numbers 1R01HD074757-01A1( U.S. NIH Grant/Contract )
1R01HD074757-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party University of Pennsylvania
Study Sponsor University of Pennsylvania
Collaborators
  • 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
PRS Account University of Pennsylvania
Verification Date June 2019