Pharmacologic Impact on Sedation Assessments (PISA)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01105663
First received: March 31, 2010
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Pediatric Acute Lung Injury
Other: Pharmacokinetic Sampling and pharmacogenetic analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacologic Impact on Sedation Assessment

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • 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. [ Time Frame: 36-48 months ] [ Designated as safety issue: Yes ]
    This is a pharmacokinetic, pharmacogenetic and pharmacodynamic study examining heritable (specific polymorphisms) on drug exposure, metabolite formation and pharmacodynamic response.


Secondary Outcome Measures:
  • 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. [ Time Frame: 36-48 months ] [ Designated as safety issue: Yes ]
    Polymorphisms in drug metabolizing systems.


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.


Enrollment: 175
Study Start Date: March 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Subjects must be enrolled in the parernt study RESTORE, be at least 10kg, and be receiving either morphine and/or midazolam continuous infusions.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105663

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Athena Zuppa, MD MSCE Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01105663     History of Changes
Other Study ID Numbers: 10-007453, R01HL098087-01
Study First Received: March 31, 2010
Last Updated: January 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
sedated
intubated
mechanically ventilated
pediatric
lung injury

Additional relevant MeSH terms:
Acute Lung Injury
Respiratory Distress Syndrome, Adult
Lung Injury
Wounds and Injuries
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Thoracic Injuries

ClinicalTrials.gov processed this record on July 29, 2014