Pharmacologic Impact on Sedation Assessments

Completed

• Conditions: Pediatric Acute Lung Injury
• Interventions: Other: Pharmacokinetic Sampling and pharmacogenetic analysis

• Registration Number: NCT01105663
• Lead Sponsor: Children's Hospital of Philadelphia

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.

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2010-03-31
• Study First Submitted QC: 2010-04-15
• Study First Posted: 2010-04-16
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-26
• Last Update Posted: 2017-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 175

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Sedated, Intubated, Morphine	Pharmacokinetic Sampling and pharmacogenetic analysis	Subjects will receive morphine/midazolam as part of clinical care. Pharmacokinetic and pharmacogenetic sampling and pharmacodynamic monitoring will occur as indicated. Pharmacokinetic samples will be assayed in the laboratory of the Division of Clinical Pharmacology and Therapeutics. Pharmacogenetic samples will be assayed in the laboratory of the Center for Applied Genomics at CHOP.
Sedated, Intubated, Midazolam	Pharmacokinetic Sampling and pharmacogenetic analysis	Subjects will receive morphine/midazolam as part of clinical care. Pharmacokinetic and pharmacogenetic sampling and pharmacodynamic monitoring will occur as indicated. Pharmacokinetic samples will be assayed in the laboratory of the Division of Clinical Pharmacology and Therapeutics. Pharmacogenetic samples will be assayed in the laboratory of the Center for Applied Genomics at CHOP.

Primary Outcome Measures

Name	Time	Method
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.	36-48 months	This is a pharmacokinetic, pharmacogenetic and pharmacodynamic study examining heritable (specific polymorphisms) on drug exposure, metabolite formation and pharmacodynamic response.

Secondary Outcome Measures

Name	Time	Method
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.	36-48 months	Polymorphisms in drug metabolizing systems.

Trial Locations

Locations (1)

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States