Preemptive Genotyping and Pain Management

Pain Clinical Trial

Official title:

Preemptive Genotyping of Children and Adolescents at Risk for Surgery and Subsequent Pain Management

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01813695
• Other study ID #: 2013-0853
• Secondary ID: NIH 3U01 HG00682
• Status: Completed
• Start date: March 2013
• Est. completion date: December 30, 2022

Study information

• Verified date: February 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to see if testing for genes related to pain and pain management before surgery affects how patients are treated for pain after surgery. The investigators want to know if this information will be used to effectively treat patients for pain after surgery if the clinical staff have a chance to review it before the surgery.

Description:

Purpose: To determine the feasibility of preemptive (preoperative) cytochrome P450 isoenzyme (CYP2D6) testing and the variability of clinical measures (postoperative) in children whose opioid selection and dosing is influenced by preemptive CYP2D6 testing compared to children whose pain management does not include CYP2D6 preemptive testing. Results from this pilot study will inform a future study investigating the utility of preemptive pharmacogenomic testing in children at risk for requiring inpatient acute pain management with opioids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 576
• Est. completion date: December 30, 2022
• Est. primary completion date: November 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

Inclusion Criteria:

• Children, 6-17 years of age and adults, 18 - 21 years with idiopathic scoliosis and/or pectus excavatum scheduled for surgical clinic visit

• BMI < 30

• Cognitively able to use a 0 - 10 numerical rating scale (NRS) to report level of pain

• Parents give permission (and children give assent when appropriate) or adult participants give consent for CYP2D6 results to be placed in Cincinnati Children's Hospital Medical Center (CCHMC's) EPIC

Exclusion Criteria:

• • Who had prior surgery for idiopathic scoliosis and/or pectus excavatum

• Who have prior CYP2D6 testing or Genetic Pharmacology Service (GPS) Psychiatry Panel documented in EPIC

• Who are taking prescription medication known to inhibit or induce CYP2D6

• Who are taking prescription medication known to inhibit (e.g. voriconazole) or induce (e.g. carbamazepine and rifampin) CYP3A4

• Who have liver or renal failure

• Who have history of narcotic abuse

Related Conditions & MeSH terms

• Pain

Intervention

Procedure:
• Preemptive genotyping in medical record

• Genotyping not included in electronic medical record

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

References & Publications (46)

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Gramke HF, de Rijke JM, van Kleef M, Raps F, Kessels AG, Peters ML, Sommer M, Marcus MA. The prevalence of postoperative pain in a cross-sectional group of patients after day-case surgery in a university hospital. Clin J Pain. 2007 Jul-Aug;23(6):543-8. doi: 10.1097/AJP.0b013e318074c970. — View Citation

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Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin North Am. 2005 Mar;23(1):21-36. doi: 10.1016/j.atc.2004.11.013. — View Citation

Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, Carleton B, Hayden MR, Madadi P, Koren G. More codeine fatalities after tonsillectomy in North American children. Pediatrics. 2012 May;129(5):e1343-7. doi: 10.1542/peds.2011-2538. Epub 2012 Apr 9. — View Citation

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Lam J, Kelly L, Ciszkowski C, Landsmeer ML, Nauta M, Carleton BC, Hayden MR, Madadi P, Koren G. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr. 2012 Jan;160(1):33-7.e2. doi: 10.1016/j.jpeds.2011.06.050. Epub 2011 Aug 31. — View Citation

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Sadhasivam S, Boat A, Mahmoud M. Comparison of patient-controlled analgesia with and without dexmedetomidine following spine surgery in children. J Clin Anesth. 2009 Nov;21(7):493-501. doi: 10.1016/j.jclinane.2008.12.017. — View Citation

Sadhasivam S, Cohen LL, Szabova A, Varughese A, Kurth CD, Willging P, Wang Y, Nick TG, Gunter J. Real-time assessment of perioperative behaviors and prediction of perioperative outcomes. Anesth Analg. 2009 Mar;108(3):822-6. doi: 10.1213/ane.0b013e318195c115. — View Citation

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Smith HS. The metabolism of opioid agents and the clinical impact of their active metabolites. Clin J Pain. 2011 Nov-Dec;27(9):824-38. doi: 10.1097/AJP.0b013e31821d8ac1. — View Citation

Sommer M, de Rijke JM, van Kleef M, Kessels AG, Peters ML, Geurts JW, Gramke HF, Marcus MA. The prevalence of postoperative pain in a sample of 1490 surgical inpatients. Eur J Anaesthesiol. 2008 Apr;25(4):267-74. doi: 10.1017/S0265021507003031. Epub 2007 Dec 6. — View Citation

Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S, Hoeft A, Stuber F. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain. 2003 Sep;105(1-2):231-8. doi: 10.1016/s0304-3959(03)00212-4. — View Citation

Voepel-Lewis T, Marinkovic A, Kostrzewa A, Tait AR, Malviya S. The prevalence of and risk factors for adverse events in children receiving patient-controlled analgesia by proxy or patient-controlled analgesia after surgery. Anesth Analg. 2008 Jul;107(1):70-5. doi: 10.1213/ane.0b013e318172fa9e. — View Citation

von Baeyer CL, Spagrud LJ, McCormick JC, Choo E, Neville K, Connelly MA. Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children's self-reports of pain intensity. Pain. 2009 Jun;143(3):223-227. doi: 10.1016/j.pain.2009.03.002. Epub 2009 Apr 8. — View Citation

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White PF, Kehlet H. Improving postoperative pain management: what are the unresolved issues? Anesthesiology. 2010 Jan;112(1):220-5. doi: 10.1097/ALN.0b013e3181c6316e. No abstract available. — View Citation

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* Note: There are 46 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Association between specific genotypes and pain sensitivity, reported postoperative pain, and opioid response	To explore association between specific genotypes (in addition to CYP2D6) and pain sensitivity, reported postoperative pain, and opioid response (pain reduction and incidence of adverse drug reactions (ADRs))	Postoperative surgery, up to two weeks
Primary	Feasibility of PreEmptive Genotyping Testing	The Investigator will use descriptive and summary statistics to determine the feasibility of preemptive CYP2D6 testing in children evaluated during a clinic visit for potential surgery.	From initial clinic visit to post-operative discharge, expected average of three months
Secondary	Analgesia Effectiveness	Pain score (NRS 0 - 10) before and after each oral opioid dose (we will use time between the before and after pain score measures as a covariate)	Admission for surgery, up to two weeks
Secondary	Analgesia Toxicity	At least 1 documented ADR; Total number of documented ADRs; Total number of ADR related responses in "Pain Medicine Report" answered "sometimes" or "always"; Total number of documented GI related ADRs - nausea (yes/no) and vomiting (yes/no); Total number of documented central nervous system (CNS) ADRs (Modified Ramsay scores > 4 and respiratory rate (RR) indicative of respiratory depression; and oxygen saturations (SpO2) < 90% on room air; and need for supplemental oxygen; and response of "always" for "Pain Medicine Report" question, "When you took the pain medicine, how often did it make you fall asleep?"	Admission for surgery, up to two weeks
Secondary	Analgesia Effectiveness	Participant related responses in "Pain Medicine Report"	Admission for surgery, up to two weeks
Secondary	Analgesia Effectiveness	Total number of rescue IV pain medication doses	Admission for surgery, up to two weeks
Secondary	Analgesia Effectiveness	Total number of concomitant analgesic adjunct medications such as muscle relaxants, acetaminophen.	Admission for surgery, up to two weeks
Secondary	Analgesia Effectiveness	Total mg/kg 24hr dose of oral opioids	Admission for surgery, up to two weeks