Randomized and Open-label Clinical Trial for Personalized Prescription of Opioid Analgesics in Postoperative Pain

Abstract

Introduction: Postoperative pain (POP) is common, often undertreated, and increases the risk of chronic pain development. Treatment involves the use of opioids for moderate to severe pain, but there is variability in response, partly due to variations in the CYP2D6 gene. Personalized prescription based on pharmacogenetics can optimize POP management, minimizing risks, and increasing effectiveness.Objectives: To evaluate the effectiveness of pharmacogenetic-guided prescription in the effectiveness and safety of opioid treatment.Methods: An open, randomized clinical trial to be conducted between 2024 and 2026. A total of 231 eligible individuals for elective surgeries will be included. Participants will be randomized into two groups: personalized prescription (PP) and control (C). The groups will undergo six mandatory visits (V1, V2, V3, V4, V5, V6) and one optional visit (V7). V1 will be conducted before surgery. Biodemographic, clinical data, and biological samples for genotyping will be collected. The level of pain will be analyzed using the Visual Analogue Scale (VAS). V2 will be conducted within 24 hours after surgery. For the PP group, personalized prescription will be based on CYP2D6 genotype, while the C group will follow the standard prescription. V3-V6 will be conducted daily after surgery for evaluating pain using the VAS. V7 will be conducted 3 months after surgery only with patients that were discharged with a prescription of opioid to measure the development of chronic pain. In V7, adherence and quality of life will also be evaluated. Genotyping will involve the extraction of genomic DNA using the Wizard® genomic DNA purification Kit (Promega, São Paulo, Brasil) as per the manufacturer's instructions. Genotyping will be performed for genetic variants of CYP2D6 using TaqMan" assays (Applied Biosystems, Massachusetts, USA). Genotype-based recommendations will be made following clinical pharmacogenetic guidelines for opioids and described drug interactions. Statistical comparison will be made between the PP and C groups regarding the relative risk of adverse drug reactions (ADRs) and pain scores using the VAS.Expected Results: It is expected that the personalized prescription process will reduce the incidence of ADRs due to opioid use and increase the effectiveness of opioid treatment.