Integrated, Individualized, and Intelligent Prescribing (I3P) Clinical Trial Network

一体化、个体化、智能处方（I3P）临床试验网络

• 批准号: 10822651
• 负责人: Kerri Cavanaugh
• 金额: $ 72.46万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-06 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822651
• 关键词: APOL1 gene; Acute; Acute Pain; Adult; Adverse effects; Affect; African American population; African ancestry; Antidepressive Agents; Behavior; Biological; Blood Pressure; Chronic Kidney Failure; Clinical; Clinical Trials; Clinical Trials Network; Data; Diagnosis; Disparity; Genetic Risk; Genomic medicine; Genotype; Guidelines; Health; Healthcare; High Prevalence; Hypertension; Individual; Intelligence; Kidney; Kidney Failure; Knowledge; Mental Depression; Opiate Addiction; Opioid; Outcome; Pain; Pain management; Participant; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Pilot Projects; Population; Population Heterogeneity; Postoperative Pain; Provider; Randomized; Risk; Safety; Selection for Treatments; Testing; blood pressure control; chronic pain; clinically relevant; cost effective; cost effectiveness; demographics; economic impact; effective therapy; genetic information; genetic testing; genetic variant; health care service utilization; health difference; high risk; hypertension control; improved; patient population; pharmacogenetic testing; primary endpoint; prospective; recruit; risk minimization; secondary analysis; secondary outcome; social determinants

The promise of genomic medicine to transform healthcare and improve health will not be fully realized until discoveries become relevant to and available for use by diverse populations and their clinicians. As part of the IGNITE II network, we are proposing two prospective randomized pragmatic genotype-guided clinical trials (GUARDD-US and ADOPT-PGx) to determine the impact of implementing genetic testing on hypertension, depression, and pain therapies. GUARDD-US: Chronic kidney disease (CKD) is associated with hypertension. People with African ancestry (AAs) have the highest risk of CKD and kidney failure, the highest prevalence of hypertension, and the lowest rate of blood pressure (BP) control. While this disparity is in part due to social determinants, ancestry has biological underpinnings and APOL1 high-risk genetic variants, nearly exclusive found in AAs, increase kidney failure risk 10-fold. We propose a genotype-guided trial to determine the effect of early vs. delayed knowledge of a positive APOL1 genotyping result on 3-month systolic blood pressure (SBP). The trial aims to recruit 5435 African Americans with hypertension, with or without CKD, randomized to immediate versus delayed return of APOL1 genetic testing. In those who are APOL1 negative, we will also conduct a pilot study to test the impact of pharmacogenetic (PGx) testing on SBP. Secondary outcomes include 6-month SBP, in CKD patients, on medications ordered, renal diagnosis and testing patient psycho-behavioral outcomes, cost effectiveness, and the effect of PGX guided hypertension management on SBP. ADOPT-PGx: Pain and depression are conditions that impact substantial proportions of the US population. The treatment of acute and chronic pain is challenged by the difficulty of finding effective therapies while minimizing the risk of adverse effects or opioid addiction. For depression, there are few clinically relevant predictors of successful treatment, which results in inadequate therapy for many patients. Both opioid and antidepressant prescriptions can be guided by PGx data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC). We propose a prospective randomized pragmatic genotype-guided clinical trial that tests the effect of genotype-guided therapy in three scenarios of patients: acute post-surgical pain, chronic pain, and depression. For each scenario, participants will be randomized to genotype-guided drug therapy versus usual approaches to drug therapy selection. Changes in patient reported outcomes representing pain and depression control using standard PROMIS scales define the primary endpoints. Secondary analyses include safety endpoints, changes in overall well-being, and economic impact represented by differences in healthcare utilization. We expect the successful results from these clinical trials will provide critical evidence needed to drive the implementation of genomic medicine across broad demographics of patient populations.

基因组医学改变医疗保健和改善健康的承诺将不会完全实现， 发现变得与不同人群及其临床医生相关并可供其使用。的一部分 IGNITE II网络，我们提出了两个前瞻性随机实用基因型指导的临床试验 （GUARDD-US和ADOPT-PGx）以确定实施基因检测对高血压的影响， 抑郁症和疼痛治疗。 GUARDD-US：慢性肾脏病（CKD）与高血压相关。非洲裔 (AAs)CKD和肾衰竭的风险最高，高血压的患病率最高， 血压（BP）控制率。虽然这种差异部分是由于社会决定因素，但血统 生物学基础和APOL 1高风险遗传变异，几乎只在AA中发现， 失败风险10倍。我们提出了一个基因型指导的试验，以确定早期与延迟知识的影响 3个月收缩压（SBP）的阳性APOL 1基因分型结果。该试验旨在招募5435名 患有高血压（伴或不伴CKD）的非裔美国人，随机分配至立即与延迟恢复治疗组 APOL 1基因检测对于APOL 1阴性的患者，我们还将进行一项试点研究，以测试其影响 SBP的药物遗传学（PGx）检测。次要结局包括CKD患者的6个月SBP， 订购的药物，肾脏诊断和测试患者心理行为结果，成本效益，以及 PGX指导下的高血压管理对SBP的影响。 ADOPT-PGx：疼痛和抑郁是影响大部分美国人群的疾病。 急性和慢性疼痛的治疗受到难以找到有效疗法的挑战， 最大限度地减少副作用或阿片类药物成瘾的风险。对于抑郁症，很少有临床相关的 成功治疗的预测因素，这导致许多患者的治疗不足。阿片类药物和 抗抑郁药处方可以由PGx数据指导，该数据基于临床研究的现有指南。 药物遗传学实施联盟（CPIC）。我们提出了一个前瞻性的随机务实 基因型指导的临床试验，测试基因型指导的治疗在三种患者情况下的效果： 急性术后疼痛、慢性疼痛和抑郁症。对于每种情况，受试者将被随机分配至 基因型指导的药物治疗与药物治疗选择的常规方法。报告的患者变化 使用标准PROMIS量表表示疼痛和抑郁控制的结果定义了主要的 端点。次要分析包括安全性终点、总体健康状况的变化和经济影响 以医疗保健利用率的差异为代表。 我们希望这些临床试验的成功结果将提供推动 在广泛的患者人群中实施基因组医学。