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

NCT ID: NCT03534063

Last Updated: 2023-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-07
• Study Completion Date: 2020-04-29

Brief Summary

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.

Detailed 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.

Conditions

Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CYP2D6-guided opioid therapy

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%.

Group Type: ACTIVE_COMPARATOR

CYP2D6-guided opioid therapy

Intervention Type: GENETIC

Using a standardized consult note, recommendations were made to avoid tramadol, hydrocodone, codeine, and oxycodone in PMs, IMs, and UMs and to use an alternative opioid (e.g. morphine, hydromorphone) or non-opioid (e.g. NSAID). Consideration of tramadol as the first-line opioid will be recommended for NMs.

Usual Care

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

CYP2D6-guided opioid therapy

Using a standardized consult note, recommendations were made to avoid tramadol, hydrocodone, codeine, and oxycodone in PMs, IMs, and UMs and to use an alternative opioid (e.g. morphine, hydromorphone) or non-opioid (e.g. NSAID). Consideration of tramadol as the first-line opioid will be recommended for NMs.

Intervention Type: GENETIC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida Health

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Larisa Cavallari, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Health at the University of Florida

Gainesville, Florida, United States

Unversity of Florida

Gainesville, Florida, United States

UF Health Orthopaedic--Villages

Summerfield, Florida, United States

Countries

United States

References

Thomas CD, Parvataneni HK, Gray CF, Deen JT, Prieto HA, Pulido LF, Elsey AR, Elwood EN, Starostik P, Gong Y, Fillingim RB, Johnson JA, Cavallari LH. A hybrid implementation-effectiveness randomized trial of CYP2D6-guided postoperative pain management. Genet Med. 2021 Apr;23(4):621-628. doi: 10.1038/s41436-020-01050-4. Epub 2021 Jan 8.

Reference Type: RESULT

PMID: 33420349 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

UL1TR001427-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OCR17562

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201800445

Identifier Type: -

Identifier Source: org_study_id