Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, Florida, USA.
Clin Transl Sci. 2022 Oct;15(10):2479-2492. doi: 10.1111/cts.13376. Epub 2022 Aug 4.
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.
术后疼痛管理中阿片类药物的处方开具具有挑战性，这是因为患者之间阿片类药物反应存在差异，且存在阿片类药物成瘾的担忧。曲马多、氢可酮和可待因依赖细胞色素 P450 2D6（CYP2D6）酶形成高效代谢物。CYP2D6 活性降低或缺失的个体（即中间代谢物[IM]或弱代谢物[PM]）具有较低浓度的高效阿片类代谢物，可能无法充分控制疼痛。这项前瞻性、多中心、随机实用试验的主要目的是确定术后 CYP2D6 指导的阿片类药物处方对疼痛控制和阿片类药物使用的影响。多达 2020 名年龄≥8 岁、计划接受手术的参与者将被纳入并随机分配至立即进行药物遗传学检测并进行临床决策支持（CDS）以指导 CYP2D6 表型指导的术后疼痛管理（干预组）或延迟检测而无 CDS（对照组）。CDS 通过医疗记录警报和/或药剂师咨询说明提供。对于干预组中的 IM 和 PM，CDS 包括避免使用氢可酮、曲马多和可待因的建议。术后 10 天和 1、3、6 个月收集患者报告的疼痛相关结局。在干预组（n=152）和对照组（n=152）中 IM 和 PM 的亚组中，主要结局为术后 10 天的疼痛强度和阿片类药物使用的复合指标，将进行比较。次要终点包括处方止痛药误用评分和 6 个月时的阿片类药物持续使用。这项试验将提供有关 CYP2D6 表型指导的阿片类药物选择改善术后疼痛控制和降低阿片类药物相关风险的临床实用性数据。
