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| ID | Type | Description | Link |
|---|---|---|---|
| U01HG010225 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Human Genome Research Institute (NHGRI) | NIH |
| University of Florida | OTHER |
| Vanderbilt University Medical Center | OTHER |
| Indiana University |
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This study is comprised of three separate pharmacogenetic trials grouped into a single protocol due to similarities in the intervention, the hypotheses, and the trial design. The three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial. Participants can enroll in only one of the three trials. All three trials were registered on ClinicalTrials.gov under NCT04445792. In July 2023 each of the three treatment trials was registered under a separate NCT# and NCT04445792 was converted to a screening record per recent guidance on master protocol research programs (MPRPs). This record is specific to the Acute Pain Trial within the ADOPT-PGx protocol.
The Acute Pain Trial is a prospective, multicenter, two arm randomized pragmatic trial. Participants meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic testing and genotype-guided post-surgical opioid therapy (Intervention arm) or standard care and pharmacogenetic testing after 6 months (Control arm). The investigators will test the hypothesis that pharmacogenetic testing and genotype guided pain management therapy improves pain control after surgery in participants who's body processes some pain medicines slower than normal.
Pain and depression are conditions that impact substantial proportions of the US population. Finding safe and effective drug therapies for both conditions is challenging. In the case of treatment for acute and chronic pain, the challenge is finding effective therapy while minimizing adverse effects or opioid addiction (and the ensuing consequences). For depression, there are few clinically relevant predictors of successful treatment leading to multiple trials of inadequate therapy for some patients. Both opioid and antidepressant prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC).
This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic setting.
The rationale for examining a genotype-guided approach to acute and chronic pain management is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and hydrocodone and data from a pilot study supporting improved pain control in intermediate and poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline. Similarly, the rationale for examining a genotype-guided approach to depression medication therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19 oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials support the hypothesis of improved depression symptom control in a genotype-guided arm.
Study objectives:
Determine if a genotype-guided approach to acute post-surgical pain therapy leads to improved pain control compared to usual care, as defined by a decrease in the SIA score. Secondarily, The investigators will evaluate whether this approach leads to reduced use of DEA Schedule II opioids and reduced pain intensity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute Pain - Immediate PGx Testing | Experimental | Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider |
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| Acute Pain - Delayed PGx Testing | Other | Delayed genetic testing of CYP2D6 and return of results after the conclusion of the 6-month follow-up period |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacogenetic testing | Other | Genetic testing of CYP2D6 and CYP2C19 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 10 Day Silverman Integrated Analgesic Assessment (SIA) Score | 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. | Day of surgery (baseline) to 10 days post surgery |
| Measure | Description | Time Frame |
|---|---|---|
| 10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale | 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. | 10 days post-surgery |
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Inclusion Criteria:
Acute Pain Trial
Exclusion Criteria
Trial-wide:
Acute Pain Trial
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| Name | Affiliation | Role |
|---|---|---|
| Hrishikesh Chakraborty | Duke University | Study Director |
| Larisa H. Cavallari, PharmD | University of Florida | Principal Investigator |
| Julie A. Johnson, PharmD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nemours Children's Health System | Wilmington | Delaware | 19803 | United States | ||
| University of Florida - Gainesville |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35899435 | Background | Cavallari LH, Cicali E, Wiisanen K, Fillingim RB, Chakraborty H, Myers RA, Blake KV, Asiyanbola B, Baye JF, Bronson WH, Cook KJ, Elwood EN, Gray CF, Gong Y, Hines L, Kannry J, Kucher N, Lynch S, Nguyen KA, Obeng AO, Pratt VM, Prieto HA, Ramos M, Sadeghpour A, Singh R, Rosenman M, Starostik P, Thomas CD, Tillman E, Dexter PR, Horowitz CR, Orlando LA, Peterson JF, Skaar TC, Van Driest SL, Volpi S, Voora D, Parvataneni HK, Johnson JA; IGNITE Pragmatic Trials Network. Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators. Clin Transl Sci. 2022 Oct;15(10):2479-2492. doi: 10.1111/cts.13376. Epub 2022 Aug 4. | |
| 41719044 |
| Label | URL |
|---|---|
| Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 23, 2024 |
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| OTHER |
| Icahn School of Medicine at Mount Sinai | OTHER |
Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy
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| Clinical decisions support | Other | Prescribing recommendations to the provider based on the pharmacogenetic testing results |
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| Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day | Opioid usage from surgery to 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. | Day of surgery (baseline) to 10 days post surgery |
| 3 Month Prescription Pain Medication Misuse | 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. | 3 months post surgery |
| 1 Month PROMIS Mobility Score | 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. | 1 month post surgery |
| Number of Participants With Opioid Persistence | 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. | 3-6 months post-surgery, assessed at 6 months |
| Participants With Drug-Gene Concordance | 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 | Within 10 days post-surgery |
| Gainesville |
| Florida |
| 32610 |
| United States |
| Nemours Children's Health System | Jacksonville | Florida | 32207 | United States |
| Nemours Children's Health System | Orlando | Florida | 32827 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Sanford Health | Fargo | North Dakota | 58104 | United States |
| Meharry Medical College | Nashville | Tennessee | 37208 | United States |
| Nashville General Hospital | Nashville | Tennessee | 37208 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Result |
| Cavallari LH, Myers RA, Chakraborty H, Skaar TC, Gray CF, Baye JF, Volpi S, Rider R, Cicali EJ, Elwood EN, Harris EC, Hines LJ, Nahid NA, Nguyen KA, Obeng AO, Parr JA, Ramos MA, Orlando LA, Prieto HA, Sadeghpour A, Singh R, Starostik P, Tillman EM, Wyatt C, Horowitz CR, Voora D, Blake KV, Parvataneni HK, Fillingim RB, Dexter PR, Peterson JF, Johnson JA; IGNITE Pragmatic Trials Network. CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial. JAMA Netw Open. 2026 Feb 2;9(2):e2558299. doi: 10.1001/jamanetworkopen.2025.58299. |
| CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial | View source |
| FG001 |
| 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 |
| COMPLETED |
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| NOT COMPLETED |
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ITT refers to the Intent To Treat population, while mITT, a subset of ITT, refers to the modified Intent To Treat population. The mITT population is the primary analytical population for the Acute Pain Trial defined as participants with a CYP2D6 activity score ≤0.75.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Intent to Treat population | Mean | Standard Deviation | years |
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| Age, Continuous | Modified Intent to Treat population | Mean | Standard Deviation | years |
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| Sex: Female, Male | Intent to Treat population | Count of Participants | Participants |
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| Sex: Female, Male | Modified Intent To Treat population | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Intent to Treat population | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Modified Intent to Treat population | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Intent to Treat population | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Modified Intent to Treat population | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 10 Day Silverman Integrated Analgesic Assessment (SIA) Score | 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. | Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75. | Posted | Mean | Standard Deviation | score on a scale | Day of surgery (baseline) to 10 days post surgery |
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| Secondary | 10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale | 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. | Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75. | Posted | Mean | Standard Deviation | score on a scale | 10 days post-surgery |
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| Secondary | Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day | Opioid usage from surgery to 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. | Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75. | Posted | Median | Inter-Quartile Range | MME/day | Day of surgery (baseline) to 10 days post surgery |
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| Secondary | 3 Month Prescription Pain Medication Misuse | 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. | 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. | Posted | Mean | Standard Deviation | T-score | 3 months post surgery |
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| Secondary | 1 Month PROMIS Mobility Score | 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | 1 month post surgery |
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| Secondary | Number of Participants With Opioid Persistence | 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. | Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75. | Posted | Count of Participants | Participants | 3-6 months post-surgery, assessed at 6 months |
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| Secondary | Participants With Drug-Gene Concordance | 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 | Modified intent to treat (mITT) population, consisting of participants who completed their surgery and have a genotypic or phenoconverted CYP2D6 activity score ≤ 0.75. | Posted | Count of Participants | Participants | Within 10 days post-surgery |
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Up to 6 months
Per the study protocol, only Adverse Device Effect (ADE) events suspected to be related to the specimen collection, laboratory assay genotyping results, and phenoconversion recommendations from the Best Practice Alerts (BPAs)/Consult notes were collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 1 | 801 | 0 | 801 | 0 | 801 |
| EG001 | 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 | 2 | 801 | 0 | 801 | 0 | 801 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hrishikesh Chakraborty, PhD | Duke University | 919-668-1238 | hrishikesh.chakraborty@duke.edu |
| Mar 25, 2025 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 14, 2023 | Nov 14, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D059787 | Acute Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000071185 | Pharmacogenomic Testing |
| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |
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