Pharmacogenomics Analysis of Morphine Pharmacokinetics in Pediatric Tonsillectomy and Adenoidectomy

NCT00836264 | Completed

• 1 other identifier: 08-007023
• Study Type: observational
• Target: 878
• Locations: 1 country
• Sites: 1

Brief Summary

Intravenous (IV) morphine requirement for immediate postoperative pain control depends upon the complex interplay of patient history, wound severity, environment, and genetics. Even for relatively uniform stimulus intensity, such as that associated with tonsillectomy and adenoidectomy (T\&A), there can be marked individual variability in response to morphine. Some patients are refractory to standard doses and need increased amounts. Others are sensitive, require less drug to attain acceptable pain levels, and/or experience unwanted side effects that limit dosing. A significant number must be switched to different analgesics altogether. Despite the long clinical history of morphine as a postoperative analgesic, researchers have only begun to examine the origins of response variability. The investigators will look at 2000 retrospective Tonsillectomy and Adenoidectomy (T\&A) cases and using this data and incorporating additional patient, surgical, and environmental factors that may contribute to response variability, the investigators then propose a prospective genome-wide association (GWA) study of 1500 children ages 4 to 18 years treated with IV morphine sulfate for day surgery T\&A.

Conditions

Tonsillectomy; Adenoidectomy; Pharmacokinetics

Keywords

Morphine; Phenotype; Genotype; Tonsillectomy; Adenoidectomy; Opioid Receptors; Genome-Wide Association; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be to identify genetic variants that contribute to the variability of morphine analgesic response following pediatric day surgery T&A.

  2 years

Study Arms (1)

Morphine T & A

Subjects ages 4-18 years of age who have a Tonsillectomy and Adenoidectomy and receive morphine for pain control and who have also enrolled in the CAG study at CHOP, "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the CHOP IRB, 2006-7-4886.

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children having Tonsillectomy and Adenoidectomy procedures done at The Children's Hospital of Philadelphia, at the Main Hospital and also at the satellite surgical centers, who have also consented to participate in "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the CHOP IRB, 2006-7-4886.

You may qualify if:

• Concurrent enrollment in the GCPD study (IRB 2006-7-4886)
• Scheduled for day surgery T\&A with expected same day discharge at CHOP Main in Philadelphia, Pennsylvania (PA) or the CHOP Ambulatory Surgical Facilities (ASFs) in Chalfont, PA; Exton, PA; or Voorhees, New Jersey (NJ)
• Male or female, age 4 - 18 years, all races and ethnic backgrounds
• Able to self-report pain on the Faces Pain Scale - Revised (FPS-R).
• Informed consent as addendum to GCPD consent document
• Assent for children ≥7 years of age

You may not qualify if:

• Parents/guardians or subjects who, in the opinion of the investigator, may be non-compliant with study schedules or procedures
• Non-English speaking subjects or parents. The reliability of the morphine analgesic requirement phenotype could be adversely affected by subtle communication differences between subjects and nursing staff assessing pain and administering morphine during patient recovery should language barriers exist. Parents must also be fluent in English as they will be at the bedside shortly after their child's arrival in recovery and could influence how their child understands pain scoring and how they interact with the nursing and research staff.
• Those parents/guardian or subjects not consenting to, or willing to participate in the GCPD study (IRB 2006-7-4886).
• Patients \< 4 y of age were excluded to improve phenotype reliability. Due to a higher empirical risk of postoperative obstruction following T\&A, children \< 4 years of age are admitted for overnight observation. The titration of morphine is more difficult in these patients as clinicians generally follow more restrictive dosing regimens and the total morphine dose is drawn out over an extended period. Furthermore, the self-report Faces Pain Scale - Revised (FPS-R) has been validated for children ≥ 4 y and will be used to corroborate the morphine response phenotypes that are primarily based on morphine doses administered to achieve low Face, Legs, Activity, Cry, Consolability (FLACC) scores. The latter behavioral scoring is required for early morphine administration as children and adolescents emerging from anesthesia may have difficulty expressing themselves in the first 30 min. In addition, it is important for the study statistical analysis to have a sequential scoring system over time that is applicable to all ages. Finally, the incidence of emergence agitation/delirium, a clinical phenomenon that shares some features of pain, but becomes distinct over 15-30 minutes, is higher in younger patients. (Sikich, 2004; Vlajkovic, 2007) By excluding children \< 4 years Investigators decrease the proportion of subjects whose FLACC scores may be high on the basis of emergence agitation/delirium.
• Significant comorbid conditions requiring a non-standard anesthetic regimen such as a history of severe post-operative nausea and vomiting requiring propofol infusion, a total intravenous anesthestic (TIVA) technique and/or mandating planned post-operative hospital admission.
• Documented allergy or adverse reaction to morphine in the patient.
• Use of opioids (e.g. codeine, oxycodone, morphine, hydromorphone) within the previous month.
• Use of non-steroidal anti-inflammatory agents or acetaminophen in the 3 days preceding the T\&A. No acetaminophen will be included in the premedication regimen on the day of surgery.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Children's Anesthesiology Associates, Ltd.: collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

PK plasma samples will be obtained

Study Officials

• Scott Cook-Sather, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 2, 2009
• First Posted: February 4, 2009
• Study Start: January 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: April 2, 2019

Record last verified: 2019-03

Locations

US (1)