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

NCT03534063 | Completed Results

• 3 other identifiers: IRB201800445UL1TR001427-04OCR17562
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 3

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.

Conditions

Pain, Postoperative

Keywords

Arthroplasty Surgery; Genotype-Guided Pain Management

Outcome Measures

Primary Outcomes (4)

• Percentage of Patients Who Agreed to Participate

  The feasibility of clinical implementation was measured by the percentage of approached patients who agreed to be the study. This was measured by the number of patients approached and the number of patients who enrolled in the study.

  12 months

• Percentage of Participants With a Clinical Phenotype Warranting Alternative Therapy

  The feasibility of implementing a genotype-guided opioid prescribing approach for participants undergoing an elective surgical procedure was analyzed by the percentage of participants in the genotype-guided arm and usual care arm with a high-risk CYP2D6 phenotype. CYP2D6 phenotypes were based on CYP2D6 genotype and phenoconversion. High-risk CYP2D6 phenotypes were poor metabolizers (PM), intermediate metabolizers (IM), ultrarapid metabolizers (UM), and ranged phenotypes such as normal to ultrarapid metabolizers and intermediate to ultrarapid metabolizers.

  An average of 2 weeks after genotype sample collection

• Percentage of Participants in the Genotype-guided Arm for Whom a Clinical Phenotype-guided Recommendation Was Accepted by the Clinician

  The feasibility of clinical implementation was measured by the percentage of participants in the genotype-guided arm for whom a clinical phenotype-guided recommendation was accepted by the clinician. Study recommendations were considered accepted for participants with a high-risk phenotype if an alternative opioid (e.g., hydromorphone, morphine) was prescribed. For CYP2D6 normal metabolizers (NM), consult recommendations were accepted if tramadol was prescribed. Participants were typically prescribed a tramadol-based regimen where in most cases hydrocodone, or another opioid, was prescribed concomitantly with tramadol as is usual practice at the clinics where participants were enrolled. Participants whose genotype resulted after the preoperative appointment were excluded from the analysis of acceptance of consult recommendations. Data for this outcome were only collected from participants in the genotyped-guided arm with CYP2D6 results returned prior to the preoperative appointment.

  An average of 2 months after genotype results returned

• Opioid Utilization

  Opioid consumption was calculated as the difference between participant-reported opioid pills prescribed at the preoperative appointment and opioid pills remaining at the 2-week time point. This difference was calculated for each opioid and then expressed as morphine milligram equivalents (MME) using standard conversion factors and the medication strength of the prescribed opioid analgesic. If a participant was prescribed multiple opioids, MMEs were calculated for each opioid and then summed to give a total MME value.

  2 weeks after surgery

Secondary Outcomes (1)

• Composite Pain Intensity

  2 weeks after surgery

Study Arms (2)

CYP2D6-guided opioid therapy

ACTIVE COMPARATOR

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%.

Genetic: CYP2D6-guided opioid therapy

Usual Care

NO INTERVENTION

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.

Interventions

CYP2D6-guided opioid therapy 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.

CYP2D6-guided opioid therapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• University of Florida Health: collaborator

Study Sites (3)

UF Health at the University of Florida

Gainesville, Florida, 32610, United States

Location

Unversity of Florida

Gainesville, Florida, 32611, United States

Location

UF Health Orthopaedic--Villages

Summerfield, Florida, 34491, United States

Location

Related Publications (1)

• 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.

  PMID: 33420349 RESULT

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Limitations and Caveats

Assessment of MME may be considered exploratory. Reliance on participant reported opioid consumption restricts MME analysis to those who successfully completed the two-week survey. Participants could have received any number of analgesics at various doses, reliance on participant responses was key to calculating MME at the follow-up timepoints, and incomplete participant-reported data reduces the available sample to assess postoperative opioid consumption.

Results Point of Contact

• Title: Dr. Larisa Cavallari
• Organization: University of Florida

LCavallari@cop.ufl.edu

(352) 273-8245

Study Officials

• Larisa Cavallari, PharmD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 23, 2018
• Study Start: June 7, 2018
• Primary Completion: April 29, 2020
• Study Completion: April 29, 2020
• Last Updated: July 17, 2023
• Results First Posted: July 17, 2023

Record last verified: 2023-07

Locations

US (3)