TonsillectomyNCT00836264
Pharmacogenomics Analysis of Morphine Pharmacokinetics in Pediatric Tonsillectomy and Adenoidectomy
An observational study of Tonsillectomy and Adenoidectomy, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Tonsillectomy, Adenoidectomy, Pharmacokinetics
- How many people
- 878 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Nov 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pharmacogenomic Analysis of Morphine Pharmacokinetics and Response Variability Following Pediatric Tonsillectomy and Adenoidectomy: A Genome-Wide Association Approach
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.
Read the detailed description
Morphine Tonsilectomy and Adenoidectomy (T\&A) Pharmacokinetics (PK) study will be done as a part of the larger institutional Center for Applied Genomics (CAG) project entitled "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the Children's Hospital of Philadelphia (CHOP) IRB, 2006-7-4886. By combining Genome Wide Association (GWA) and PK data, we wish to conduct a Pharmacogenomic (PG) study of IV morphine administered as standard of care during and after pediatric day surgery T\&A. Because we expect several genes to play a role in the morphine response, we must use a large, relatively uniform pediatric surgical population such that for T\&A. Through observation and minimal-risk blood sampling of this cohort of children, we hope to identify genetic variants that predict analgesic response to (and serum levels of) morphine sulfate. Pediatric patients ages 4-18 y, presenting with significant tonsillar/adenoidal tissue hypertrophy, sleep disordered breathing and/or recurrent infection, and requiring T\&A are eligible. Morphine is the most common IV analgesic used for T\&A at the Children's Hospital of Philadelphia (CHOP). As is necessary for accurately defining analgesic response phenotype, morphine will be administered in a structured manner consistent with standard of care at this institution. As defined below, children resistant to morphine (MR) and those sensitive to it (MS) will be identified as specific phenotypes to be compared with normal responders (NR) in a GWA study.
This study begins with a retrospective electronic database query of 2000 day surgery T\&A cases between 11/1/2005 and 10/31/2008 in which morphine was used as the sole IV analgesic. Data from this portion of the study will help us refine phenotype parameters, should robust subpopulations of response types emerge, and provide background information required for eventual project funding by the National Institutes of Health (NIH). The prospective portion of the study will follow an additional 1650 children newly enrolled in the CAG study and now presenting for T\&A.
- Conditions
- Tonsillectomy, Adenoidectomy, Pharmacokinetics
- Keywords
- Morphine, Phenotype, Genotype, Tonsillectomy, Adenoidectomy, Opioid Receptors, Genome-Wide Association, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be to identify genetic variants that contribute to the variability of morphine analgesic response following pediatric day surgery T&A.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TonsillectomyStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 878 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Anesthesiology Associates, Ltd.
- Responsible party
- Sponsor
- Investigators
- Scott Cook-Sather, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00836264
- Sponsor's protocol ID
- 08-007023
- Status last verified
- Mar 2019
- First submitted
- 2 Feb 2009
- Last updated
- 2 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomic Analysis of Morphine Pharmacokinetics and Response Variability Following Pediatric Tonsillectomy and Adenoidectomy: A Genome-Wide Association Approach
- ClinicalTrials.gov ID
- NCT00836264
- Acronym / sponsor ID
- 08-007023
- Conditions
- Tonsillectomy, Adenoidectomy, Pharmacokinetics
- Keywords
- Morphine, Phenotype, Genotype, Tonsillectomy, Adenoidectomy, Opioid Receptors, Genome-Wide Association, Pharmacokinetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 878 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Children's Anesthesiology Associates, Ltd.
- Study start
- Jan 2009 (actual)
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 4 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Morphine Tonsilectomy and Adenoidectomy (T\&A) Pharmacokinetics (PK) study will be done as a part of the larger institutional Center for Applied Genomics (CAG) project entitled "A Study of the Genetic Causes of Complex Pediatric Disorders" (GCPD study), as approved by the Children's Hospital of Philadelphia (CHOP) IRB, 2006-7-4886. By combining Genome Wide Association (GWA) and PK data, we wish to conduct a Pharmacogenomic (PG) study of IV morphine administered as standard of care during and after pediatric day surgery T\&A. Because we expect several genes to play a role in the morphine response, we must use a large, relatively uniform pediatric surgical population such that for T\&A. Through observation and minimal-risk blood sampling of this cohort of children, we hope to identify genetic variants that predict analgesic response to (and serum levels of) morphine sulfate. Pediatric patients ages 4-18 y, presenting with significant tonsillar/adenoidal tissue hypertrophy, sleep disordered breathing and/or recurrent infection, and requiring T\&A are eligible. Morphine is the most common IV analgesic used for T\&A at the Children's Hospital of Philadelphia (CHOP). As is necessary for accurately defining analgesic response phenotype, morphine will be administered in a structured manner consistent with standard of care at this institution. As defined below, children resistant to morphine (MR) and those sensitive to it (MS) will be identified as specific phenotypes to be compared with normal responders (NR) in a GWA study.
This study begins with a retrospective electronic database query of 2000 day surgery T\&A cases between 11/1/2005 and 10/31/2008 in which morphine was used as the sole IV analgesic. Data from this portion of the study will help us refine phenotype parameters, should robust subpopulations of response types emerge, and provide background information required for eventual project funding by the National Institutes of Health (NIH). The prospective portion of the study will follow an additional 1650 children newly enrolled in the CAG study and now presenting for T\&A.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The primary endpoint will be to identify genetic variants that contribute to the variability of morphine analgesic response following pediatric day surgery T&A.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Cook-Sather, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tonsillectomy and Adenoidectomy, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint will be to identify genetic variants that contribute to the variability of morphine analgesic response following pediatric day surgery T&A. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2019.