Trial Outcomes & Findings for Implementing Genomics in Practice (IGNITE): CYP2D6 Genotype-Guided Pain Management in Patients Undergoing Arthroplasty Surgery (NCT NCT03534063)

Last Updated: 2023-07-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

260 participants

Primary outcome timeframe

12 months

Results posted on

2023-07-17

Participant Flow

Participant milestones

Participant milestones
Measure	Genotype-guided Opioid Therapy For participants randomized to the genotype-guided arm, a CYP2D6 phenotype and pharmacist consult note will be provided to physicians to assist in opioid prescribing.	Usual Care For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.
Overall Study STARTED	173	87
Overall Study COMPLETED	154	80
Overall Study NOT COMPLETED	19	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The participants included in the analysis were the ones who received the allocated intervention (surgery).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Genotype-guided Opioid Therapy n=154 Participants For participants randomized to the genotype-guided arm, a CYP2D6 phenotype and pharmacist consult note will be provided to physicians to assist in opioid prescribing.	Usual Care n=80 Participants For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.	Total n=234 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Age, Categorical Between 18 and 65 years	61 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	40 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	101 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Age, Categorical >=65 years	93 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	40 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	133 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Sex: Female, Male Female	91 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	46 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	137 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Sex: Female, Male Male	63 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	34 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	97 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) Asian	3 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	1 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	4 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	12 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	28 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) White	131 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	65 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	196 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) More than one race	4 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	2 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	6 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	0 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).
Region of Enrollment United States	154 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	80 Participants n=7 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).	234 Participants n=5 Participants • The participants included in the analysis were the ones who received the allocated intervention (surgery).

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Participants Approached for the Study, Prior to Randomization n=282 Participants Total count of participants approached to enroll into the study, prior to randomization.	Usual Care For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.
Percentage of Patients Who Agreed to Participate Agreed to participant and enrolled into the study	260 Participants	—
Percentage of Patients Who Agreed to Participate Declined to participant in the study	22 Participants	—

PRIMARY outcome

Timeframe: An average of 2 weeks after genotype sample collection

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

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.

Outcome measures

Outcome measures
Measure	Participants Approached for the Study, Prior to Randomization n=154 Participants Total count of participants approached to enroll into the study, prior to randomization.	Usual Care n=74 Participants For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.
Percentage of Participants With a Clinical Phenotype Warranting Alternative Therapy High-Risk CYP2D6 Phentoype	35 Participants	28 Participants
Percentage of Participants With a Clinical Phenotype Warranting Alternative Therapy Normal CYP2D6 Phenotype	119 Participants	46 Participants

PRIMARY outcome

Timeframe: An average of 2 months after genotype results returned

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

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.

Outcome measures

Outcome measures
Measure	Participants Approached for the Study, Prior to Randomization n=29 Participants Total count of participants approached to enroll into the study, prior to randomization.	Usual Care n=115 Participants For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.
Percentage of Participants in the Genotype-guided Arm for Whom a Clinical Phenotype-guided Recommendation Was Accepted by the Clinician	21 Participants	101 Participants

PRIMARY outcome

Timeframe: 2 weeks after surgery

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

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.

Outcome measures

Outcome measures
Measure	Participants Approached for the Study, Prior to Randomization n=126 Participants Total count of participants approached to enroll into the study, prior to randomization.	Usual Care n=68 Participants For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.
Opioid Utilization	200 morphine milligram equivalents Interval 104.0 to 280.0	230 morphine milligram equivalents Interval 133.0 to 350.0

SECONDARY outcome

Timeframe: 2 weeks after surgery

Population: Participants that completed the pain intensity survey 2 weeks after surgery

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.

Outcome measures

Outcome measures
Measure	Participants Approached for the Study, Prior to Randomization n=137 Participants Total count of participants approached to enroll into the study, prior to randomization.	Usual Care n=74 Participants For participants randomized to the usual care arm, providers will follow usual care prescribing practices for post operative opioid prescribing.
Composite Pain Intensity	2.6 units on a scale Standard Deviation 0.8	2.5 units on a scale Standard Deviation 0.7

Adverse Events

Genotype-guided Opioid Therapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Usual Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Larisa Cavallari

University of Florida

Phone: (352) 273-8245

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place