Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the <scp>IGNITE ADOPT PGx</scp> investigators

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

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Publication Details

Journal
Clinical and Translational Science
Published
2024-08-01
DOI
https://doi.org/10.1111/cts.70005
Citations
6
Primary Topic
Pain Management and Placebo Effect
Type
article
Field-Weighted Citation Impact
2.06
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article

Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators

Rajbir Singh, Sheryl Lynch, Simona Volpi, Todd C. Skaar et al.
6 citations
Clinical and Translational Science
Pain Management and Placebo Effect
2.06
article

Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators

Rajbir Singh, Sheryl Lynch, Simona Volpi, Todd C. Skaar, Rachel A. Myers, Paul Richard Dexter, Geoffrey S. Ginsburg, Erica N. Elwood, John Thomas Callaghan, Deepak Voora, Azita Sadeghpour, Saskia Shuman, Victoria M. Pratt, Aniwaa Owusu Obeng, Carol R. Horowitz, Almut G. Winterstein, Hrishikesh Chakraborty, Michael T. Eadon, Emily J. Cicali, Larisa H. Cavallari, Roger Benton Fillingim, Haesuk Park, Emma M. Tillman, Marc B. Rosenman, Sara L. Van Driest, Julie Ann Johnson, Josh F. Peterson, Lori A. Orlando, Khoa A. Nguyen, Kristin Wiisanen
article en
6 citations

Abstract

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

Clinical and Translational ScienceVol. 17(8)
Northwestern University (US), Meharry Medical College (US), Lurie Children's Hospital (US), National Institutes of Health (US), Mount Sinai Health System (US), Regenstrief Institute (US), Center for Drug Evaluation and Research (US), Duke University (US), Institute for Family Health (US), University of Florida (US), National Human Genome Research Institute (US), Indiana University School of Medicine, Indiana University – Purdue University Indianapolis (US), Vanderbilt University Medical Center (US), Florida College (US), Icahn School of Medicine at Mount Sinai (US)
Good health and well-being
Openalex Percentile: Top 13%
Pain Management and Placebo Effect
2.06
DOIOpen Access PDFOpenAlex
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