Pharmacologic Impact on Sedation Assessments (PISA)

Children's Hospital of Philadelphia (CHOP)

Status: Completed

Conditions: Pediatric Acute Lung Injury

Treatments: Other: Pharmacokinetic Sampling and pharmacogenetic analysis

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT01105663

R01HL098087-01 (U.S. NIH Grant/Contract)

10-007453

Details and patient eligibility

About

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.

Full 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.

Enrollment: 175 patients

Sex: All

Ages: 1 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

175 participants in 2 patient groups

Sedated, Intubated, Morphine

Description:

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.

Treatment:

Other: Pharmacokinetic Sampling and pharmacogenetic analysis

Sedated, Intubated, Midazolam

Description:

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.

Treatment:

Other: Pharmacokinetic Sampling and pharmacogenetic analysis