Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood (RESTORE-cog)
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| ClinicalTrials.gov Identifier: NCT02225041 |
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Recruitment Status :
Completed
First Posted : August 25, 2014
Last Update Posted : June 18, 2019
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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:
- 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.
- 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 |
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| Intellectual Disability Perceptual Disorders Memory Disorders |
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 |
| Actual Enrollment : | 360 participants |
| Observational Model: | Case-Control |
| Time Perspective: | Cross-Sectional |
| Official Title: | Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood |
| Actual Study Start Date : | August 2014 |
| Actual Primary Completion Date : | December 2018 |
| Actual Study Completion Date : | December 2018 |
- 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 ]
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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 |
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.
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
Show 31 study locations
| 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 |
| 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: | June 18, 2019 |
| Last Verified: | June 2019 |
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intensive care critical care child family survivors |
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Intellectual Disability Memory Disorders Perceptual Disorders Disease Critical Illness Pathologic Processes |
Disease Attributes Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Neurodevelopmental Disorders Mental Disorders |