IGNITE Cost Extension - Admin Supplement

项目摘要 目前的行政补充请求是延长24个月，并提供资金以完成正在进行的 IGNITE网络实用临床试验，GUARDD-US和采用-PGx。GUARDD-US和收养-PGx， 分别于2020年7月和2021年2月开始实施。这些试验将有助于确定影响 对高血压、抑郁症和疼痛治疗实施基因测试。GUARDD-US：慢性肾脏 疾病(CKD)与高血压有关。非洲血统(AA)的人患CKD的风险最高 和肾衰竭，高血压患病率最高，血压控制率最低。 虽然这种差异在一定程度上是由社会决定因素造成的，但血统是有生物学基础的，而APOL1高- 仅在AA中发现的风险基因变异会使肾衰竭风险增加10倍。我们提出了一个基因分型- 指导试验，以确定早期和延迟知晓阳性APOL1基因结果对3- 一个月的收缩压(SBP)。这项临床试验旨在招募患有高血压的非裔美国人， 或者没有CKD，随机进行APOL1基因检测的立即返回和延迟返回。在那些 在APOL1阴性的情况下，我们还将进行一项初步研究，以测试药物遗传学(PGx)测试对SBP的影响。 领养-PGx：疼痛和抑郁是影响相当大比例美国人口的疾病。这个 急慢性疼痛的治疗面临着难以找到有效疗法的挑战，同时最大限度地减少 不良反应或阿片成瘾的风险。对于抑郁症，几乎没有临床上相关的预测因子 成功的治疗，导致许多患者的治疗不充分。我们提出了一个预期的 随机实用的基因引导的临床试验，测试基因引导治疗在三个国家的效果 患者的情景：手术后急性疼痛、慢性疼痛和抑郁。对于每个方案，参与者将 随机接受基因引导的药物治疗，而不是通常的药物治疗选择方法。变化 在患者报告的结果中，使用标准的Promis量表定义了疼痛和抑郁的控制 主端点。二次分析包括安全终点，总体幸福感的变化，以及 医疗保健利用的差异所代表的经济影响。有资金的24个月延期是 由于启动每个试用时出现意外的全网延迟以及因新冠肺炎而关闭，因此需要此服务。这个 本行政补编所要求的经费反映了试验需要以及额外招收50名 抑郁症试验的参与者，以解决其他群体的招聘不足问题和费用 与15份二手稿件的主要分析和出版费用有关。

Project Summary The current administrative supplement request is for a 24-month extension with funding to complete the ongoing IGNITE Network pragmatic clinical trials, GUARDD-US and ADOPT-PGx. The GUARDD-US and ADOPT-PGx, have been underway since July 2020 and February 2021, respectively. These trials will help 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, exclusively 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 clinical trial aims to recruit 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. 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. 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. A 24-month extension with funding is needed due to unanticipated network-wide delays in launching each trial and shutdowns due to COVID-19. The funding requested in this administrative supplement reflects the trial needs as well as enrollment of 50 additional participants for the Depression Trial to address recruitment shortfalls by other groups and for the costs associated with leading analyses and publication costs for 15 secondary manuscripts.