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The Effect of General Anesthesia on Pharmacokinetics of Oxycodone in Pediatric

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ClinicalTrials.gov Identifier: NCT03054831
Recruitment Status : Recruiting
First Posted : February 16, 2017
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Patcharee Sriswasdi, Boston Children’s Hospital

Brief Summary:
Oxycodone is an oral opioid analgesic that is most commonly prescribed for the management of pain in post-operative patients at Boston Children's Hospital. Oxycodone has been widely used in adults and children to relieve post-operative pain. However, its pharmacokinetics (what it does in the body) and pharmacodynamics (how it works) have not been well established in children. Some children, because of their specific genetic make-up, may metabolize the drug more quickly and therefore may be at risk for more side effects in the commonly prescribed dose. The investigators would like to find out more about how general anesthesia (GA) effects how this drug is absorbed, metabolized and excreted in children. In order to study these aspects, the investigators would like to give oxycodone to surgical patients (group one will receive oxycodone at the beginning of GA and group two will receive oxycodone at the end of GA) at Boston Children's Hospital then measure its metabolic activity and also perform a specific genetic analysis.

Condition or disease Intervention/treatment Phase
Liquid Oxycodone Drug: liquid oxycodone Phase 4

Detailed Description:

This research will involve two treatment groups: (children 2-5 years old) and (children 6-8 years old). The first group will include 20 children 2-5 years old. In this group the children will be randomized to either receive 0.1mg/kg of liquid oxycodone via an orogastric (OG) tube after induction but before the procedure at the beginning of general anesthesia, or 0.1mg/kg of liquid oxycodone via an OG tube after the procedure at the end of general anesthesia. Every patient will receive inhalational or intravenous induction of anesthesia as decided by the anesthesia team on the day of surgery, as is routine clinical care. An intravenous cannula (IV) will be inserted in every patient as part of their routine clinical care. No additional intravenous line will be required for this study. An arterial line will only be used if indicated by surgical procedure. As part of the study protocol, a blood sample (5 mL) will be taken from the IV and sent for genetic analysis. The genetic testing is specifically to analyze the following genotypes only: cytochrome P450 (CYP) 2D6 and 3A4, which represent the differences in cytochrome P450 metabolism of oxycodone. An orogastric tube will be placed in the stomach (placement verified by routine accepted clinical guidelines) under anesthesia as is part of standard routine clinical care to remove gastric contents. The same orogastric tube will be used for intragastric liquid oxycodone administration in a dose of 0.1 mg/kg either before the procedure (beginning of general anesthesia) or after the procedure (end of general anesthesia). This weight-adjusted dose of 0.1 mg/kg is administered as per standard clinical dosing guidelines at Boston Children's Hospital..

The second group will include 20 patients (children 6-8 years old). In this group the children will be randomize to either receive 0.1 mg/kg of liquid oxycodone per oral (PO) before the surgery in pre-op holding, or 0.1 mg/kg of liquid oxycodone PO after surgery in the Post Anesthesia Care Unit (PACU).

As part of routine clinical care, the anesthesiologist may give any of the following narcotics for additional pain management based on their clinical judgment: Fentanyl, sufentanil, and remifentanyl. For the purposes of this study, the following narcotics will not be administered: morphine and hydromorphone. Additionally, oxycodone will not be administered after the initial study dose in the operating room. These medications produce metabolites that would interfere with the pharmacokinetics being studied. Furthermore, morphine, hydromorphone and oxycodone will be withheld during the entire study period (up to 24 hours). This is not standard clinical care, but withholding morphine/hydromorphone/oxycodone will not result in any additional risk for the patient, since there are equally effective pain management options available which are standard of care. If the clinician deems that morphine, hydromorphone, or oxycodone is necessary for clinical care, it will not be withheld, and the patient will be withdrawn from the study.

A total of 11 blood samples will be drawn for the study. The first sample will be sent for genetic testing. The other 10 samples will be drawn at the following time points: sample 1: within 2 hours of post dose oxycodone, sample 2-7: within 30 to 90 min after last sample drawn and within 12 hours post dose oxycodone, sample 8-10: anytime between 12 to 24 hours post dose oxycodone (assigned as clinically indicated based on duration of surgery to minimize patient disturbance). Therefore, blood samples (1 mL each) will be drawn at 10 different time points in each patient. Blood for the study purposes will be drawn from the existing intravenous line or arterial line at the specific time points indicated when the child is under anesthesia. Postoperatively, regarding the timing of the blood draws, it is not necessary to be exact but rather to accurately record the time that the sample is taken. Thus, this will be coordinated with the drawing of routine laboratory tests if possible, in order to minimize patient discomfort.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of General Anesthesia on Pharmacokinetics and Pharmacogenomics of Liquid Oxycodone in Pediatric Surgical Patients
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Age 2-5 years-Before GA
The group will include 25 patients (children 2-5 years old). In this group the children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube before the procedure at the beginning of general anesthesia (after intubation).
Drug: liquid oxycodone

The group will include 25 patients (children 2-5 years old). In this group the children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube before the procedure at the beginning of general anesthesia (after intubation).

In this group 25 children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube after the procedure at the end of general anesthesia (before extubation).

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally before the surgery in pre-op holding.

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally after surgery in the Post Anesthesia Care Unit (PACU).


Active Comparator: Age 2-5 years-After GA
In this group 25 children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube after the procedure at the end of general anesthesia (before extubation).
Drug: liquid oxycodone

The group will include 25 patients (children 2-5 years old). In this group the children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube before the procedure at the beginning of general anesthesia (after intubation).

In this group 25 children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube after the procedure at the end of general anesthesia (before extubation).

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally before the surgery in pre-op holding.

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally after surgery in the Post Anesthesia Care Unit (PACU).


Active Comparator: Age 6-8 years-Before GA
The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally before the surgery in pre-op holding.
Drug: liquid oxycodone

The group will include 25 patients (children 2-5 years old). In this group the children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube before the procedure at the beginning of general anesthesia (after intubation).

In this group 25 children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube after the procedure at the end of general anesthesia (before extubation).

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally before the surgery in pre-op holding.

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally after surgery in the Post Anesthesia Care Unit (PACU).


Active Comparator: Age 6-8 years-After GA
The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally after surgery in the Post Anesthesia Care Unit (PACU).
Drug: liquid oxycodone

The group will include 25 patients (children 2-5 years old). In this group the children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube before the procedure at the beginning of general anesthesia (after intubation).

In this group 25 children will be randomized to receive 0.1mg/kg of liquid oxycodone via an orogastric tube after the procedure at the end of general anesthesia (before extubation).

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally before the surgery in pre-op holding.

The group will include 25 patients (children 6-8 years old). In this group the children will be randomize to receive 0.1 mg/kg of liquid oxycodone orally after surgery in the Post Anesthesia Care Unit (PACU).





Primary Outcome Measures :
  1. the effect of general anesthesia on plasma oxycodone level in patients age 2-5 years . [ Time Frame: upto 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine the area under the curve(AUC)

  2. the effect of general anesthesia on plasma oxycodone level in patients age 6-8 years [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine the area under the curve(AUC)


Secondary Outcome Measures :
  1. the effect of general anesthesia on plasma oxymorphone level in patients age 2-5 years [ Time Frame: up to 2 years ]
    Plasma oxymorphone levels, at 10 time points, will be used to determine the area under the curve(AUC)

  2. the effect of general anesthesia on plasma noroxymorphone in patients age 2-5 years [ Time Frame: up to 2 years ]
    Plasma noroxymorphone levels, at 10 time points, will be used to determine area under the curve(AUC)

  3. the effect of general anesthesia on plasma noroxycodone level in patients age 2-5 years [ Time Frame: up to 24 weeks ]
    Plasma noroxycodone levels, at 10 time points, will be used to determine the area under the curve(AUC)

  4. the effect of general anesthesia on plasma oxymorphone level in patients age 6-8 years [ Time Frame: up to 24 weeks ]
    Plasma oxymorphone levels, at 10 time points, will be used to determine the area under the curve(AUC)

  5. the effect of general anesthesia on plasma noroxymorphone in patients age 6-8 years [ Time Frame: up to 24 weeks ]
    Plasma noroxymorphone levels, at 10 time points, will be used to determine area under the curve(AUC)

  6. the effect of general anesthesia on plasma noroxycodone level in patients age 6-8 years [ Time Frame: up to 24 weeks ]
    Plasma noroxycodone levels, at 10 time points, will be used to determine the area under the curve(AUC)

  7. the effect of general anesthesia on plasma oxycodone level in patients age 2-5 years with respect to the pharmacogenomics. [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine the area under the curve(AUC).

  8. the effect of general anesthesia on plasma oxycodone level in patients age 6-8 years years with respect to the pharmacogenomics. [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine the area under the curve(AUC).

  9. the effect of general anesthesia on oxycodone absorption in patients age 2-5 years [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine the onset of oxycodone absoprtion

  10. the effect of general anesthesia on oxycodone absorption in patients age 6-8 years [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine the onset of oxycodone absoprtion

  11. the effect of general anesthesia on maximum plasma oxycodone level in patients age 2-5 years [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine maximum plasma concentration (Cmax).

  12. the effect of general anesthesia on maximum plasma oxycodone level in patients age 6-8 years [ Time Frame: up to 24 weeks ]
    Plasma oxycodone levels, at 10 time points, will be used to determine maximum plasma concentration (Cmax).



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Ages Eligible for Study:   2 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients are scheduled for the following in-patient surgical procedures:

  • hypospadias repair
  • ureteral reimplantation
  • pyeloplasty (Genitourinary Surgery Service) and age between 2-8 years, and opioid naive, and not meet exclusion criteria

Exclusion Criteria:

  • currently taking cytochrome P450(CYP) 3A4 or 2D6 inhibitors/inducers
  • known history of allergy to oxycodone
  • known gastrointestinal, hepatic, or renal dysfunction
  • known sleep apnea or impaired respiratory reserve
  • speak a language other than English

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03054831


Contacts
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Contact: Patcharee Sriswasdi, MD, MPH 617-355-7737 patcharee.sriswasdi@childrens.harvard.edu
Contact: Christine Dube, MS, BSN 617-355-6185 christine.dube@childrens.harvard.edu

Locations
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United States, Massachusetts
Boston Children Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Christine Dube, MS, BSN, RN    617-355-6185    Christine.Dube@childrens.harvard.edu   
Principal Investigator: Patcharee Sriswasdi, MD         
Sponsors and Collaborators
Boston Children’s Hospital
Investigators
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Principal Investigator: Patcharee Sriswasdi, MD, MPH Boston Children’s Hospital

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Responsible Party: Patcharee Sriswasdi, Attending Anesthesiologist, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT03054831     History of Changes
Other Study ID Numbers: IRB-P00022355
First Posted: February 16, 2017    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Anesthetics
Oxycodone
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Opioid
Narcotics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents