Pharmacologic Impact on Sedation Assessments (PISA)
This study is currently recruiting participants.
Verified June 2013 by Children's Hospital of Philadelphia
Sponsor:
Children's Hospital of Philadelphia
Collaborator:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01105663
First received: March 31, 2010
Last updated: June 5, 2013
Last verified: June 2013
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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 |
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.
| Estimated Enrollment: | 500 |
| Study Start Date: | March 2010 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | August 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:
|
|
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:
|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01105663
Contacts
| Contact: Athena Zuppa, MD MSCE | 2674267359 | zuppa@email.chop.edu |
| Contact: Janice Prodell, RN | 2155904924 | prodell@email.chop.edu |
Locations
| United States, Pennsylvania | |
| The Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact: Athena F Zuppa, MD MSCE 215-590-5505 zuppa@email.chop.edu | |
| Contact: Janice Prodell, RN 215-590-4924 prodell@email.chop.edu | |
| Principal Investigator: Athena Zuppa, MD MSCE | |
| Sub-Investigator: Jeffrey Barrett, PhD | |
| Sub-Investigator: Hakon Hakonarson, MD PhD | |
| Sub-Investigator: Martha A Q Curley, RN PhD FAAN | |
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: | June 5, 2013 |
| 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 Lung Diseases |
Respiratory Tract Diseases Respiration Disorders Thoracic Injuries Wounds and Injuries |
ClinicalTrials.gov processed this record on June 18, 2013