Pharmacologic Impact on Sedation Assessments

NCT01105663 | Completed DMC

• 2 other identifiers: 10-007453R01HL098087-01
• Study Type: observational
• Target: 175
• Locations: 1 country
• Sites: 1

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.

Conditions

Pediatric Acute Lung Injury

Keywords

sedated; intubated; mechanically ventilated; pediatric; lung injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

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

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

Interventions

Pharmacokinetic Sampling and pharmacogenetic analysis OTHER

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.

Also known as: Pharmacokinetic Sampling, pharmacogenetic Sampling

Sedated, Intubated, Midazolam; Sedated, Intubated, Morphine

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

The primary evaluation will be the assessment of morphine/midazolam pharmacokinetics (PK) and pharmacodynamics (PD). Data from all fully evaluable subjects will be included in the analysis. Analyses will be model based.

MeSH Terms

Conditions

Lung Injury

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Thoracic Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Athena Zuppa, MD MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2010
• First Posted: April 16, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 27, 2017

Record last verified: 2017-01

Locations

US (1)