Trial Outcomes & Findings for A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Acute Pain Trial) (NCT NCT05966129)

NCT ID: NCT05966129

Last Updated: 2025-06-05

Results Overview

A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. The SIA has a total score range of -200 to 200, where a higher score corresponds with higher pain and opioid use.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

1602 participants

Primary outcome timeframe

Day of surgery (baseline) to 10 days post surgery

Results posted on

2025-06-05

Participant Flow

This record is specific to the Acute Pain Trial within the ADOPT PGx protocol. It only contains the participants consented to the Acute Pain Trial.

Participant milestones

Participant milestones
Measure
Acute Pain - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Overall Study
STARTED
801
801
Overall Study
COMPLETED
645
638
Overall Study
NOT COMPLETED
156
163

Reasons for withdrawal

Reasons for withdrawal
Measure
Acute Pain - Immediate PGx Testing
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Overall Study
Death
1
2
Overall Study
Lost to Follow-up
63
66
Overall Study
Protocol Violation
1
0
Overall Study
Withdrawal by Subject
26
25
Overall Study
Surgery not completed
63
69
Overall Study
Surgery logistics issue
2
1

Baseline Characteristics

Intent to Treat population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Acute Pain - Immediate PGx Testing
n=801 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing
n=801 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Total
n=1602 Participants
Total of all reporting groups
Age, Continuous
62.8 years
STANDARD_DEVIATION 12.1 • n=176 Participants • Modified Intent to Treat population
61.8 years
STANDARD_DEVIATION 13.1 • n=175 Participants • Modified Intent to Treat population
62.3 years
STANDARD_DEVIATION 12.6 • n=351 Participants • Modified Intent to Treat population
Sex: Female, Male
Female
116 Participants
n=176 Participants • Modified Intent To Treat population
122 Participants
n=175 Participants • Modified Intent To Treat population
238 Participants
n=351 Participants • Modified Intent To Treat population
Sex: Female, Male
Male
60 Participants
n=176 Participants • Modified Intent To Treat population
53 Participants
n=175 Participants • Modified Intent To Treat population
113 Participants
n=351 Participants • Modified Intent To Treat population
Ethnicity (NIH/OMB)
Hispanic or Latino
5 Participants
n=176 Participants • Modified Intent to Treat population
6 Participants
n=175 Participants • Modified Intent to Treat population
11 Participants
n=351 Participants • Modified Intent to Treat population
Ethnicity (NIH/OMB)
Not Hispanic or Latino
170 Participants
n=176 Participants • Modified Intent to Treat population
169 Participants
n=175 Participants • Modified Intent to Treat population
339 Participants
n=351 Participants • Modified Intent to Treat population
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
n=176 Participants • Modified Intent to Treat population
0 Participants
n=175 Participants • Modified Intent to Treat population
1 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
0 Participants
n=176 Participants • Modified Intent to Treat population
3 Participants
n=175 Participants • Modified Intent to Treat population
3 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · Asian
8 Participants
n=176 Participants • Modified Intent to Treat population
0 Participants
n=175 Participants • Modified Intent to Treat population
8 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · Native Hawaiian or Other Pacific Islander
1 Participants
n=176 Participants • Modified Intent to Treat population
1 Participants
n=175 Participants • Modified Intent to Treat population
2 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · Black or African American
22 Participants
n=176 Participants • Modified Intent to Treat population
29 Participants
n=175 Participants • Modified Intent to Treat population
51 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · White
139 Participants
n=176 Participants • Modified Intent to Treat population
134 Participants
n=175 Participants • Modified Intent to Treat population
273 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · More than one race
0 Participants
n=176 Participants • Modified Intent to Treat population
3 Participants
n=175 Participants • Modified Intent to Treat population
3 Participants
n=351 Participants • Modified Intent to Treat population
Race/Ethnicity, Customized
Race · Other
6 Participants
n=176 Participants • Modified Intent to Treat population
5 Participants
n=175 Participants • Modified Intent to Treat population
11 Participants
n=351 Participants • Modified Intent to Treat population
Region of Enrollment
United States
801 Participants
n=801 Participants
801 Participants
n=801 Participants
1602 Participants
n=1602 Participants

PRIMARY outcome

Timeframe: Day of surgery (baseline) to 10 days post surgery

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75.

A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. The SIA has a total score range of -200 to 200, where a higher score corresponds with higher pain and opioid use.

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=160 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=152 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
10 Day Silverman Integrated Analgesic Assessment (SIA) Score
1.4 score on a scale
Standard Deviation 95.9
-1.4 score on a scale
Standard Deviation 93.1

SECONDARY outcome

Timeframe: 10 days post-surgery

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75.

PROMIS (Patient-Reported Outcomes Measurement Information System) Numeric Pain Rating Scale Pain intensity at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. Pain was measured on a scale of 0-10, where higher scores correspond to higher levels of pain.

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=168 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=160 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale
5.2 score on a scale
Standard Deviation 2.2
5.1 score on a scale
Standard Deviation 2.3

SECONDARY outcome

Timeframe: Day of surgery (baseline) to 10 days post surgery

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75.

Opioid usage from surgery to 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=160 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=152 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day
10.0 MME/day
Interval 3.0 to 20.0
8.9 MME/day
Interval 3.5 to 18.4

SECONDARY outcome

Timeframe: 3 months post surgery

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75 who indicated having a prescription for pain medication in the past 3 months.

The 7-item PROMIS Prescription Pain Medication Misuse questionnaire assesses the extent to which participants experience medication misuse symptoms over the past 3 months using a 5-point Likert scale. The 7 questions are converted to a raw score, ranging from 7 to 35. Raw scores are converted to T-scores using the PROMIS conversion tables and range from 36.3 to 55.8. Higher scores reflect greater medication misuse.

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=93 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=98 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
3 Month Prescription Pain Medication Misuse
38.5 T-score
Standard Deviation 3.8
39.2 T-score
Standard Deviation 4.5

SECONDARY outcome

Timeframe: 1 month post surgery

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75 in adults only.

PROMIS mobility score at 1 month post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75 in the adult population only. The score ranges from 15 to 75, where a higher score corresponds to higher mobility.

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=164 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=161 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
1 Month PROMIS Mobility Score
40.4 score on a scale
Standard Deviation 16.6
39.4 score on a scale
Standard Deviation 17.2

SECONDARY outcome

Timeframe: 3-6 months post-surgery, assessed at 6 months

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75.

Opioid persistence defined as a filled prescription for an opioid medication 3-6 months post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75.

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=153 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=146 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Number of Participants With Opioid Persistence
24 Participants
21 Participants

SECONDARY outcome

Timeframe: Within 10 days post-surgery

Population: Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75.

Drug-Gene Concordance defined as an agreement between the Pharmacogenomics (PGx) Test and the prescribed opioids post surgery for pain management in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75

Outcome measures

Outcome measures
Measure
Acute Pain - Immediate PGx Testing (Modified Intent-to-treat, mITT)
n=176 Participants
Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results
Acute Pain - Delayed PGx Testing (Modified Intent-to-treat, mITT)
n=175 Participants
Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Participants With Drug-Gene Concordance
112 Participants
47 Participants

Adverse Events

Acute Pain - Immediate PGx Testing

Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths

Acute Pain - Delayed PGx Testing

Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Hrishikesh Chakraborty, PhD

Duke University

Phone: 919-668-1238

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place