Open AccessImplementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators
Author(s) -
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.
Publication year - 2022
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13376
Subject(s) - hydrocodone , medicine , tramadol , codeine , opioid , cyp2d6 , randomized controlled trial , clinical trial , pain ladder , clinical endpoint , pharmacogenetics , anesthesia , analgesic , oxycodone , morphine , receptor , cytochrome p450 , metabolism , biochemistry , chemistry , genotype , gene
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.