Clinical trial NCT01105663: Pharmacologic Impact on Sedation Assessments
Official title: Pharmacologic Impact on Sedation Assessment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pediatric Acute Lung Injury
Keywords: sedated
intubated
mechanically ventilated
pediatric
lung injury
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2010-04-16
Enrollment: 175
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects must be enrolled in the parent study RESTORE, be at least 10kg, and be receiving either morphine and/or midazolam continuous infusions.

Brief summary: PISA is an ancillary study to the NIH funded clinical RESTORE Trial (U01 HL086622). This study will provide data that may allow for improved dosing recommendations in this critically ill population of children.

Detailed description: PISA is an ancillary study to the NIH funded clinical RESTORE Trial (U01 HL086622). This project will use sophisticated modeling and simulation techniques to evaluate the impact of genetics and other variables such as degree of illness, age, weight and organ dysfunction on the pharmacokinetics and pharmacodynamics of morphine and midazolam in children who are mechanically ventilated for respiratory failure, and require sedation. This proposed work will allow the design of a pharmacologic model that can be used to individualize therapy in children requiring mechanical ventilation with the goal of optimizing sedation while minimizing the duration of mechanical ventilation. This study will provide data that may allow for improved dosing recommendations in this critically ill population of children.

Eligibility criteria: Inclusion Criteria:• Enrolled in RESTORE clinical trial

* Be greater than or equal to 7 kg
* Receiving morphine and/or midazolam continuous infusions
* Give Informed Consent/Assent

Exclusion Criteria:

* Intubated and mechanically ventilated for immediate post-operative care and stabilization
* Cyanotic heart disease with unrepaired or palliated right to left intracardiac shunt
* History of single ventricle at any stage of repair
* Congenital diaphragmatic hernia or paralysis
* Primary pulmonary hypertension
* Critical airway (e.g., post laryngotracheal construction) or anatomical obstruction of the lower airway (e.g., mediastinal mass)
* Ventilator dependent (including noninvasive) on Pediatric Intensive Care Unit (PICU) admission (chronic assisted ventilation)
* Neuromuscular respiratory failure
* Spinal cord injury above the lumbar region
* Pain managed by patient controlled analgesia (PCA) or epidural catheter
* Family/medical team has decided not to provide full support (patient treatment considered futile)
* Enrolled in any other sedation clinical trial concurrently or within the last 30 days
* Known allergy to any of the study medications.

Primary outcomes:
measure: In children who are mechanically ventilated, to quantitatively define the heritable factors that underlie the variability in 1) midazolam and 2) morphine exposure and response.
timeFrame: 36-48 months
Secondary outcomes:
measure: In children who are mechanically ventilated, to quantitatively define the non-heritable factors that underlie the variability in 1) midazolam and 2) morphine exposure and response.
timeFrame: 36-48 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Athena Zuppa, MD MSCE
role: PRINCIPAL_INVESTIGATOR
References: