IGNITE Cost Extension - Admin Supplement

IGNITE 成本扩展 - 管理补充

• 批准号: 10820198
• 负责人: Larisa Humma Cavallari
• 金额: $ 135.18万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10820198
• 关键词: APOL1 gene; Acute; Acute Pain; Address; Administrative Supplement; Adult; Adverse effects; African American population; African ancestry; Antidepressive Agents; Biological; Blood Pressure; COVID-19; Chronic Kidney Failure; Clinical; Clinical Trials; Data; Disparity; Dose; Effectiveness; Enrollment; Ethnic Origin; Florida; Funding; Future; Genomic medicine; Genomics; Genotype; Guidelines; Health; Healthcare; High Prevalence; Hypertension; Kidney Failure; Knowledge; Manuscripts; Mental Depression; Opiate Addiction; Opioid; Outcome; Pain; Pain management; Participant; Patient Outcomes Assessments; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pharmacotherapy; Pilot Projects; Population; Population Heterogeneity; Postoperative Pain; Pragmatic clinical trial; Provider; Publications; Race; Randomized; Risk; Safety; Selection for Treatments; Site; Test Result; Testing; Time; Universities; Vulnerable Populations; blood pressure control; chronic pain; clinically relevant; comparison control; cost; demographics; depressive symptoms; economic impact; effective therapy; genetic testing; genetic variant; health care service utilization; health difference; health disparity; high risk; hypertension control; hypertensive; improved; opioid therapy; participant enrollment; patient population; pharmacogenetic testing; primary endpoint; primary outcome; prospective; recruit; risk minimization; secondary analysis; social determinants; treatment arm; treatment as usual

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.

项目摘要 当前的行政补充要求是进行24个月的延期，并提供资金以完成正在进行的 IGNITE网络务实的临床试验，Guardd-US和Adday-PGX。 Guardd-Us和andudy-pgx， 自2020年7月和2021年2月以来一直在进行。这些试验将有助于确定影响 在高血压，抑郁和疼痛疗法上实施基因检测。 Guardd-us：慢性肾脏 疾病（CKD）与高血压有关。非洲血统（AAS）的人的CKD风险最高 和肾衰竭，高血压的最高患病率以及最低的血压（BP）控制率。 尽管这种差异部分是由于社会决定因素所致，但祖先具有生物学基础，而Apol1高 - 在AAS中仅发现的风险遗传变异，增加了肾衰竭的风险10倍。我们提出了一种基因型 - 指导性试验确定早期与延迟对阳性Apol1基因分型的知识对3-的影响 月收缩压（SBP）。该临床试验旨在招募患有高血压的非裔美国人， 或没有CKD，随机分配到立即与APOL1基因测试的延迟回报。在那些 APOL1阴性，我们还将进行一项试点研究，以测试药物遗传学（PGX）测试对SBP的影响。 采用PGX：疼痛和抑郁是影响美国人口大量比例的疾病。这 急性和慢性疼痛的治疗受到寻找有效疗法的困难而挑战 不良反应或阿片类药物成瘾的风险。对于抑郁症，几乎没有临床相关的预测因素 成功的治疗，导致许多患者的治疗不足。我们提出了一个潜在的 随机实用基因型引导的临床试验，该试验测试了基因型引导治疗在三个 患者的情况：急性手术后疼痛，慢性疼痛和抑郁。对于每种情况，参与者将 被随机分为基因型引导的药物治疗，而不是通常的药物治疗方法。更改 用标准的Promis量表定义的患者报告的结果表示疼痛和抑郁控制的结果 主要终点。次要分析包括安全终点，整体福祉的变化以及 经济影响由医疗保健利用的差异所代表。 24个月的资金延期是 由于意外的网络范围延迟，因此在启动COVID-19引起的每个试验和关闭时所需。这 此行政补品中要求的资金反映了审判需求以及50个额外的注册 抑郁症试验的参与者解决其他群体的招聘短缺以及费用 与15个二级手稿的领先分析和出版成本相关。

项目成果

Acceptability, Feasibility, and Utility of Integrating Pharmacogenetic Testing into a Child Psychiatry Clinic.

• DOI: 10.1111/cts.12914
• 发表时间: 2021-03
• 期刊: Clinical and translational science
• 作者: Claudio-Campos K;Padrón A;Jerkins G;Nainaparampil J;Nelson R;Martin A;Wiisanen K;Smith DM;Strekalova Y;Marsiske M;Cicali EJ;Cavallari LH;Mathews CA
• 通讯作者: Mathews CA

The Quest for the Optimal Periprocedural Antithrombotic Treatment Strategy in ACS Patients Undergoing PCI.

寻求接受 PCI 的 ACS 患者的最佳围手术期抗血栓治疗策略。

• DOI: 10.1016/j.jacc.2018.01.040
• 发表时间: 2018
• 期刊: Journal of the American College of Cardiology
• 影响因子: 24
• 作者: Angiolillo,DominickJ;Rollini,Fabiana;Franchi,Francesco
• 通讯作者: Franchi,Francesco

CYP2D6-guided opioid therapy for adults with cancer pain: A randomized implementation clinical trial.

CYP2D6 引导的阿片类药物治疗成人癌症疼痛：一项随机实施临床试验。

• DOI: 10.1002/phar.2875
• 发表时间: 2023
• 期刊: Pharmacotherapy
• 影响因子: 4.1
• 作者: Mosley,ScottA;Cicali,Emily;DelCueto,Alex;Portman,DianeG;Donovan,KristineA;Gong,Yan;Langaee,Taimour;Gopalan,Priya;Schmit,Jessica;Starr,JasonS;Silver,Natalie;Chang,YoungD;Rajasekhara,Sahana;Smith,JoshuaE;Soares,HeloisaP

How to Transition from Single-Gene Pharmacogenetic Testing to Preemptive Panel-Based Testing: A Tutorial.

• DOI: 10.1002/cpt.1912
• 发表时间: 2020-09
• 期刊: Clinical pharmacology and therapeutics
• 影响因子: 6.7
• 作者: Marrero RJ;Cicali EJ;Arwood MJ;Eddy E;DeRemer D;Ramnaraign BH;Daily KC;Jones D Jr;Cook KJ;Cavallari LH;Wiisanen Weitzel K;Langaee T;Newsom KJ;Starostik P;Clare-Salzer MJ;Johnson JA;George TJ;Cooper-DeHoff RM
• 通讯作者: Cooper-DeHoff RM

CYP2C19 polymorphisms and therapeutic drug monitoring of voriconazole: are we ready for clinical implementation of pharmacogenomics?

• DOI: 10.1002/phar.1400
• 发表时间: 2014-07
• 期刊: PHARMACOTHERAPY
• 影响因子: 4.1
• 作者: Obeng, Aniwaa Owusu;Egelund, Eric F.;Alsultan, Abdullah;Peloquin, Charles A.;Johnson, Julie A.
• 通讯作者: Johnson, Julie A.