Pharmacologic Impact on Sedation Assessments (PISA)

Pharmacologic Impact on Sedation Assessment

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.

Study Overview

• Status: Completed
• Conditions: Pediatric Acute Lung Injury
• Intervention / Treatment: Other: Pharmacokinetic Sampling and pharmacogenetic analysis

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 Type: Observational
• Enrollment (Actual): 175

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sedated, Intubated, Morphine; 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.	Other: Pharmacokinetic Sampling and pharmacogenetic analysis; Pharmacogenetic and pharmacokinetic samples will be obtained from a peripheral catheter, central catheter, or venipuncture coordinated with scheduled phlebotomies. Pharmacokinetic and pharmacogenetic analyses will be performed. Pharmacodynamic data will be collected.; Other Names: Pharmacokinetic Sampling; pharmacogenetic Sampling
Sedated, Intubated, Midazolam; 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.	Other: Pharmacokinetic Sampling and pharmacogenetic analysis; Pharmacogenetic and pharmacokinetic samples will be obtained from a peripheral catheter, central catheter, or venipuncture coordinated with scheduled phlebotomies. Pharmacokinetic and pharmacogenetic analyses will be performed. Pharmacodynamic data will be collected.; Other Names: Pharmacokinetic Sampling; pharmacogenetic Sampling

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Polymorphisms in drug metabolizing systems.	36-48 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Athena Zuppa, MD MSCE, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: April 15, 2010
• First Posted (Estimate): April 16, 2010

Study Record Updates

• Last Update Posted (Estimate): January 27, 2017
• Last Update Submitted That Met QC Criteria: January 26, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: pediatric; lung injury; mechanically ventilated; intubated; sedated
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 10-007453; R01HL098087-01 (U.S. NIH Grant/Contract)