Pharmacologic Impact on Sedation Assessments

Pediatric Acute Lung Injury Clinical Trial

— PISA  

Official title:

Pharmacologic Impact on Sedation Assessment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01105663
• Other study ID #: 10-007453
• Secondary ID: R01HL098087-01
• Status: Completed
• Phase: N/A
• First received: March 31, 2010
• Last updated: January 26, 2017
• Start date: March 2010
• Est. completion date: December 2013

Study information

• Verified date: January 2017
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Lung Injury
• Pediatric Acute Lung Injury
• Respiratory Distress Syndrome, Adult

Intervention

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.

Locations

Country	Name	City	State
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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