A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Acute Pain Trial)

NCT05966129 | Completed Results DMC

• 2 other identifiers: PRO00104948_AU01HG010225
• Study Type: interventional
• Target: 1,602
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Acute Pain

Keywords

Pharmacogenetic; CYP2D6; CYP2C19

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• 10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale

  10 days post-surgery

• Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day

  Day of surgery (baseline) to 10 days post surgery

• 3 Month Prescription Pain Medication Misuse

  3 months post surgery

• 1 Month PROMIS Mobility Score

  1 month post surgery

• Number of Participants With Opioid Persistence

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

Study Arms (2)

Acute Pain - Immediate PGx Testing

EXPERIMENTAL

Immediate genetic testing of CYP2D6 and clinical decisions support for pain management prescribing to the healthcare provider

Other: Pharmacogenetic testing; Other: Clinical decisions support

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

Other: Pharmacogenetic testing

Interventions

Pharmacogenetic testing OTHER

Genetic testing of CYP2D6 and CYP2C19

Acute Pain - Delayed PGx Testing; Acute Pain - Immediate PGx Testing

Clinical decisions support OTHER

Prescribing recommendations to the provider based on the pharmacogenetic testing results

Acute Pain - Immediate PGx Testing

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute Pain Trial
• Age ≥ 8 years
• English speaking or Spanish speaking
• Elective/planned surgery types with planned or anticipated to be treated with tramadol, hydrocodone, or codeine pain management at an enrolling site, which may include orthopedic surgeries (e.g. arthroplasty, spine, etc.), open abdominal surgery, or cardiothoracic surgery and others

You may not qualify if:

• Trial-wide:
• Life expectancy less than 12 months
• Are too cognitively impaired to provide informed consent and/or complete study protocol
• Are institutionalized or too ill to participate (i.e. mental or nursing home facility or incarcerated)
• Have a history of allogeneic stem cell transplant or liver transplant
• People with prior clinical pharmacogenetic test results for genes relevant for the study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for depression) or already enrolled in an ADOPT PGx trial
• Acute Pain Trial
• Undergoing a laparoscopic surgery
• Receiving chronic opioid therapy, defined as use of opioids on most days for \>3 months

Sponsors & Collaborators

• Duke University: lead
• National Human Genome Research Institute (NHGRI): collaborator
• University of Florida: collaborator
• Vanderbilt University Medical Center: collaborator
• Indiana University School of Medicine: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (11)

Nemours Children's Health System

Wilmington, Delaware, 19803, United States

Location

University of Florida - Gainesville

Gainesville, Florida, 32610, United States

Location

Nemours Children's Health System

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Health System

Orlando, Florida, 32827, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Sanford Health

Fargo, North Dakota, 58104, United States

Location

Meharry Medical College

Nashville, Tennessee, 37208, United States

Location

Nashville General Hospital

Nashville, Tennessee, 37208, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• 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.

  PMID: 35899435 BACKGROUND

• 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.

  PMID: 41719044 RESULT

Related Links

• Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators
• CYP2D6-Guided Opioid Management and Postoperative Pain Control: A Randomized Clinical Trial

MeSH Terms

Conditions

Acute Pain

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Hrishikesh Chakraborty, PhD
• Organization: Duke University

hrishikesh.chakraborty@duke.edu

919-668-1238

Study Officials

• Hrishikesh Chakraborty

  Duke University

  STUDY DIRECTOR

• Larisa H. Cavallari, PharmD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Julie A. Johnson, PharmD

  Ohio State University

  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

Model Details: Immediate vs. delayed pharmacogenetic testing and genotype-guided pain or depression therapy

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: July 28, 2023
• Study Start: March 10, 2021
• Primary Completion: March 25, 2024
• Study Completion: March 25, 2024
• Last Updated: March 19, 2026
• Results First Posted: June 5, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)