Implementing Genomics in Practice (IGNITE): CYP2D6 Genotype-Guided Pain Management in Patients Undergoing Arthroplasty Surgery

University of Florida

Status: Completed

Conditions: Pain, Postoperative

Treatments: Genetic: CYP2D6-guided opioid therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03534063

UL1TR001427-04 (U.S. NIH Grant/Contract)

IRB201800445

OCR17562 (Other Identifier)

Details and patient eligibility

About

This will be a randomized, open-labeled pilot pragmatic clinical trial. Patients undergoing arthroplasty surgery will be recruited from the University of Florida (UF) Health Gainesville and the Villages Orthopedic clinics for CYP2D6 pharmacogenetic testing to manage post-surgical pain. Patients will be randomized 2:1 to either usual care or genotype-guided care. The aims of the study were to: 1) test the feasibility of a genotype-guided opioid prescribing approach for patients undergoing an outpatient surgical procedure, a group at high risk for persistent opioid use; and 2) evaluate the effect of genotype-guided post-surgical pain management on pain control and opioid prescribing.

Full description

This study was a randomized, open-label, type 2 hybrid implementation effectiveness trial conducted to test the hypothesis that CYP2D6 genotype-guided management of post-surgical pain 1) was feasible, and 2) reduced the use of codeine, tramadol, hydrocodone, and oxycodone in Poor Metabolizers (PMs), Intermediate Metabolizers (IMs), and Ultrarapid metabolizers (UMs). In addition to the reduced use of opioids listed above, we aimed to see if participants had improved post-operative pain control in PMs/IMs and reduced Drug Enforcement Administration (DEA) Schedule II (C-II) opioids in Normal Metabolizers (NMs). Patients scheduled to undergo arthroplasty surgery were recruited from the UF Health Gainesville and the Villages Orthopedic clinics. Patients were randomized 2:1 to a genotype-guided versus usual care approach. For patients with CYP2D6 PM, IM or UM phenotype based on genotype or drug interactions, a recommendation to avoid hydrocodone, tramadol, codeine, and oxycodone were made. In NMs, tramadol was recommended, given evidence of its lower potential addiction risk than C-II opioids. Patient-Reported Outcomes Measurement Information System (PROMIS) measures were administered at baseline (within 30 days of surgery) and 2 weeks ± 4 days post-surgery for patients in each arm. Pain scores and assessments of physical functioning, emotional functioning, and mobility from the PROMIS measures and utilization of pain medications during the 2-week period following surgery were also compared between groups.

Enrollment: 260 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Scheduled to undergo total joint arthroplasty at area hospital
• Primary unilateral total hip or knee arthroplasty scheduled within approximately 6 months of the initial evaluation clinic visit

Exclusion criteria

• Patients scheduled to undergo a revision or bilateral procedure
• Receiving chronic opioid therapy, defined as the use of opioids on most days for > 3 month
• Allergy to opioids

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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260 participants in 2 patient groups

CYP2D6-guided opioid therapy

Active Comparator group

Description:

Participants randomized to the CYP2D6-guided arm will have their CYP2D6 genotyping completed prior to surgery (in the absence of any genotyping error) with results reported in the electronic health record (EHR). Patients will be categorized as CYP2D6 PM, IM, NM, or UM based on CYP2D6 genotype/activity score and FDA guidance on drug interactions. Strong inhibitors (e.g. bupropion, fluoxetine, paroxetine) phenoconvert patients to PMs, with moderate inhibitors (e.g. duloxetine, fluvoxamine) reducing CYP2D6 activity scores by 50%.

Treatment:

Genetic: CYP2D6-guided opioid therapy

Usual Care

No Intervention group

Description:

Participants randomized to the usual care arm will have their DNA collected at the start of the study and stored at the lab until after they have completed their surgery and the 2-week follow-up, at which time, their sample was genotyped with the results reported in the EHR.