Pain, PostoperativeNCT03534063

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

A study testing CYP2D6-guided opioid therapy in people with Pain, Postoperative, run by University of Florida at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Pain, Postoperative
What is being tested?: CYP2D6-guided opioid therapy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 260 participants
Where: 3 sitesUnited States
Study dates: 7 Jun 2018to 29 Apr 2020
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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 locations and contacts

3 sites in 1 country.

United States3 sites

UF Health at the University of Florida
Gainesville, Florida, 32610
Unversity of Florida
Gainesville, Florida, 32611
UF Health Orthopaedic--Villages
Summerfield, Florida, 34491

Other trials in United States

About this study

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.

Read the 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
Being tested: CYP2D6-guided opioid therapy
Keywords: Arthroplasty Surgery, Genotype-Guided Pain Management
Medical subject headings: Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CYP2D6-guided opioid therapyGenetic
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.

Study groups in NCT03534063
Study group	Role	What they receive
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%. Receives: 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 weeks after surgery

Secondary outcomes (1)

Composite Pain Intensity
Composite pain intensity was compared between the genotype-guided arm and usual care arm 2 weeks after surgery. The first two scales in the PROMIS Pain Intensity item bank assess pain intensity utilizing a 7-day recall period (items include the phrase "the past 7 days") while the third scale asks the patient to rate their pain intensity "right now." Each of the 3 scales (worst pain, average pain, and current pain) used to calculate the composite pain intensity score has a range of 1 to 5, with the following text assigned to the numeric scale, 1 -"had no pain", 2 -"mild", 3 -"moderate", 4 -"severe", and 5 -"very severe." The mean composite pain intensity ranges from 1-5. The higher the composite pain score, the more pain and thus worse outcomes.
Measured: 2 weeks after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Jun 201829 Apr 2020

First posted23 May 2018
Study start7 Jun 2018
Primary completion29 Apr 2020
Study completion29 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
More trials run by University of FloridaThe 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: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 260 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03534063
Sponsor's protocol ID: IRB201800445
Other IDs: UL1TR001427-04, OCR17562
Status last verified: Jul 2023
First submitted: 10 May 2018
Last updated: 17 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

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.
PubMed 33420349

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pain, Postoperative trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Implementing Genomics in Practice (IGNITE): CYP2D6 Genotype-Guided Pain Management in Patients Undergoing Arthroplasty Surgery
ClinicalTrials.gov ID: NCT03534063
Acronym / sponsor ID: IRB201800445
Conditions: Pain, Postoperative
Keywords: Arthroplasty Surgery, Genotype-Guided Pain Management
Study type: Interventional
Recruitment status: Completed
Enrolment: 260 participants (actual)
Lead sponsor: University of FloridaUniversity, hospital or other
Collaborators: University of Florida Health
Study start: 7 Jun 2018 (actual)
Primary completion: 29 Apr 2020 (actual)
Study completion: 29 Apr 2020 (actual)
First posted: 23 May 2018 (actual)
Results: Posted 17 Jul 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
CYP2D6-guided opioid therapy	Active comparator	Genetic: CYP2D6-guided opioid therapyParticipants 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%.
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.

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CYP2D6-guided opioid therapyUsing 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.	Genetic	CYP2D6-guided opioid therapy

Primary outcome

Percentage of Patients Who Agreed to Participate
Time frame: 12 months
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.
Percentage of Participants With a Clinical Phenotype Warranting Alternative Therapy
Time frame: An average of 2 weeks after genotype sample collection
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.
Percentage of Participants in the Genotype-guided Arm for Whom a Clinical Phenotype-guided Recommendation Was Accepted by the Clinician
Time frame: An average of 2 months after genotype results returned
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.
Opioid Utilization
Time frame: 2 weeks after surgery
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.

1 secondary outcome

Composite Pain Intensity
Time frame: 2 weeks after surgery

Results and safety

Results posted to the registry on 17 Jul 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Genotype-guided Opioid Therapy	173	154
Usual Care	87	80

Primary outcome: Percentage of Patients Who Agreed to Participate

Time frame: 12 months. Count of participants. Unit: Participants

Measure	Participants Approached for the Study, Prior to Randomization n = 282
Agreed to participant and enrolled into the study	260
Declined to participant in the study	22

Primary outcome: Percentage of Participants With a Clinical Phenotype Warranting Alternative Therapy

Time frame: An average of 2 weeks after genotype sample collection. Count of participants. Unit: Participants

Measure	Genotype-guided Opioid Therapy n = 154	Usual Care n = 74
High-Risk CYP2D6 Phentoype	35	28
Normal CYP2D6 Phenotype	119	46

Population analysed: Participants enrolled and randomized who underwent a total joint arthroplasty procedure, completed the study, and were genotyped.

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

Time frame: An average of 2 months after genotype results returned. Count of participants. Unit: Participants

Measure	High-Risk CYP2D6 Phenotype in the Genotype-guided Arm n = 29	Normal CYP2D6 Phenotype in the Genotype-guided Arm n = 115
Value	21	101

Population analysed: Participants in the genotyped-guided arm with CYP2D6 results returned prior to the preoperative appointment.

Primary outcome: Opioid Utilization

Time frame: 2 weeks after surgery. Mean (Inter-Quartile Range). Unit: morphine milligram equivalents

Measure	Genotype-guided Opioid Therapy n = 126	Usual Care n = 68
Value	200 (104 to 280)	230 (133 to 350)

Genotype-guided Opioid Therapy vs Usual Care: p = .047, Wilcoxon (Mann-Whitney)

Population analysed: Study population that completed a 2-week post-surgery follow-up survey.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse event data were not collected as a part of this study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Genotype-guided Opioid Therapy	0 of 0	0 of 0	0
Usual Care	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 33420349Thomas 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.

Related trials for Pain, Postoperative

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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.

Larisa Cavallari, PharmD principal investigator

University of Florida

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing CYP2D6-guided opioid therapy in people with Pain, Postoperative, run by University of Florida at 3 sites 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 2 inclusion and 3 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 17 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

Yes. Results are posted in the registry (first posted 17 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Patients Who Agreed to Participate (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03534063, which also lists 1 linked publication.

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 17 Jul 2023.