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 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ADOPT-PGx。GUARDD-US和ADOPT-PGx， 已分别自二零二零年七月及二零二一年二月开始进行。这些试验将有助于确定 对高血压、抑郁症和疼痛疗法进行基因检测。GUARDD-US：慢性肾脏 慢性肾脏病（CKD）与高血压有关。非洲血统（AA）的人患慢性肾病的风险最高 高血压患病率最高，血压控制率最低。 虽然这种差异部分是由于社会决定因素，但血统有生物学基础，APOL 1高- 风险遗传变异，仅在AA中发现，增加肾衰竭风险10倍。我们提出一种基因型- 指导性试验，以确定早期与延迟了解阳性APOL 1基因分型结果对3- 月收缩压（SBP）。该临床试验旨在招募患有高血压的非洲裔美国人， 或无CKD，随机分为立即与延迟返回APOL 1基因检测组。在那些 APOL 1阴性，我们还将进行一项初步研究，以检测药物遗传学（PGx）检测对SBP的影响。 ADOPT-PGx：疼痛和抑郁是影响大部分美国人群的疾病。的 急性和慢性疼痛的治疗受到了难以找到有效疗法同时最小化 副作用或阿片成瘾的风险。对于抑郁症，几乎没有临床相关的预测因子， 成功的治疗，这导致许多患者的治疗不足。我们提出了一个前瞻性的 随机实用基因型指导的临床试验，测试基因型指导治疗在三个 患者的情况：急性术后疼痛、慢性疼痛和抑郁症。对于每一个场景，参与者将 被随机分配到基因型指导的药物治疗与通常的药物治疗选择方法。变化 在使用标准PROMIS量表定义的代表疼痛和抑郁控制的患者报告结局中， 主要终点。次要分析包括安全性终点、总体健康状况的变化，以及 以医疗保健利用差异为代表的经济影响。24个月的延期和资金是 由于推出每项试验的网络范围意外延迟以及COVID-19导致的关闭，的 本行政补充文件中要求的资金反映了试验需求以及另外50例患者的入组情况。 抑郁症试验的参与者，以解决其他团体的招募不足和费用 与15份二级手稿的主要分析和出版费用有关。

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

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.

Role of genetic testing in patients undergoing percutaneous coronary intervention.

基因检测在接受经皮冠状动脉介入治疗的患者中的作用。

• DOI: 10.1080/17512433.2017.1353909
• 发表时间: 2018-03
• 期刊: Expert review of clinical pharmacology
• 影响因子: 4.4
• 作者: Moon JY;Franchi F;Rollini F;Rivas Rios JR;Kureti M;Cavallari LH;Angiolillo DJ
• 通讯作者: Angiolillo DJ

Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians.

埃及人急性冠状动脉综合征后，对氯吡格雷和阿司匹林反应的药物遗传学和临床预测指标。

• DOI: 10.1097/fpc.0000000000000349
• 发表时间: 2018-09
• 期刊: PHARMACOGENETICS AND GENOMICS
• 影响因子: 2.6
• 作者: Fathy, Shaimaa;Shahin, Mohamed H.;Langaee, Taimour;Khalil, Basma M.;Saleh, Ayman;Sabry, Nagwa A.;Schaalan, Mona F.;El Wakeel, Lamiaa L.;Cavallari, Larisa H.
• 通讯作者: Cavallari, Larisa H.