Browsing by Author "Cicali, Emily"

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    Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.
    (Wiley, 2022-07-28) Cavallari, Larisa H.; Cicali, Emily; Wiisanen, Kristin; Fillingim, Roger B.; Chakraborty, Hrishikesh; Myers, Rachel A.; Blake, Kathryn V.; Asiyanbola, Bolanle; Baye, Jordan F.; Bronson, Wesley H.; Cook, Kelsey J.; Elwood, Erica N.; Gray, Chancellor F.; Gong, Yan; Hines, Lindsay; Kannry, Joseph; Kucher, Natalie; Lynch, Sheryl; Nguyen, Khoa A.; Obeng, Aniwaa Owusu; Pratt, Victoria M.; Prieto, Hernan A.; Ramos, Michelle; Sadeghpour, Azita; Singh, Rajbir; Rosenman, Marc; Starostik, Petr; Thomas, Cameron D.; Tillman, Emma; Dexter, Paul R.; Horowitz, Carol R.; Orlando, Lori A.; Peterson, Josh F.; Skaar, Todd C.; Van Driest, Sara L.; Volpi, Simona; Voora, Deepak; Parvataneni, Hari K.; Johnson, Julie A.
    Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.
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    Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators
    (Wiley, 2024) Skaar, Todd C.; Myers, Rachel A.; Fillingim, Roger B.; Callaghan, John T.; Cicali, Emily; Eadon, Michael T.; Elwood, Erica N.; Ginsburg, Geoffrey S.; Lynch, Sheryl; Nguyen, Khoa A.; Obeng, Aniwaa Owusu; Park, Haesuk; Pratt, Victoria M.; Rosenman, Marc; Sadeghpour, Azita; Shuman, Saskia; Singh, Rajbir; Tillman, Emma M.; Volpi, Simona; Wiisanen, Kristin; Winterstein, Almut G.; Horowitz, Carol R.; Voora, Deepak; Orlando, Lori; Chakraborty, Hrishikesh; Van Driest, Sara; Peterson, Josh F.; Cavallari, Larisa A.; Johnson, Julie A.; Dexter, Paul R.; IGNITE Pragmatic Trials Network; Medicine, School of Medicine
    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.