Heart Failure Polypill in India: A Late-Stage Implementation Strategy

印度的心力衰竭复方药物：后期实施策略

基本信息

批准号：
10371464
负责人：
ANUBHA AGARWAL
金额：
$ 14.76万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-23 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10371464
关键词：
Adherence Adopted Adrenergic beta-Antagonists Adult Adverse event Age Angiotensin Receptor Area Australia Cardiomyopathies Cardiovascular Diseases Cardiovascular system Caring Chronic Chronic Disease Cities Clinical Clinical Pharmacology Clinical Trials Clinical Trials Design Collaborations Consensus Consolidated Framework for Implementation Research Country Data Collection Developing Countries Development Disease Disease Marker EFRAC Ensure Evaluation Focus Groups Funding Future Global Change Goals Guidelines HIV Health Personnel Heart Heart failure Hospitalization Hospitals Hybrids Hypertension Income India Individual Institutes Interruption Intervention Investments Kansas Left Ventricular Ejection Fraction Measures Medical Mentorship Methodology Methods Mineralocorticoid Receptor Morbidity - disease rate National Heart, Lung, and Blood Institute Natriuretic Peptides New York Outcome Participant Patient Care Patients Pharmaceutical Preparations Pharmacotherapy Phase Positioning Attribute Prevalence Process Public Health Questionnaires Randomized Clinical Trials Reach Effectiveness Adoption Implementation and Maintenance Registries Reporting Research Research Methodology Risk Factors Safety Science Series Serious Adverse Event Severity of illness Strategic vision Target Populations Time Titrations Training Training Activity Translating Treatment Failure United States United States National Institutes of Health Universities Withdrawal antagonist base burden of illness career design disorder control evidence base global health health related quality of life implementation barriers implementation evaluation implementation outcomes implementation science implementation strategy improved innovation low and middle-income countries medication compliance meetings mortality multidisciplinary novel novel strategies primary outcome process evaluation research and development secondary outcome sex socioeconomics success treatment as usual trial design

项目摘要

PROJECT SUMMARY/ABSTRACT Heart failure (HF) is a leading global public health problem. The burden of HF is increasing in low- and middle- income countries and clinical outcomes remain poor. Guideline-directed medical therapy (a combination of distinct medications from disparate drug classes) improves morbidity and mortality in patients with HF with reduced ejection fraction (HFrEF). Despite this high-quality evidence, guideline-directed medical therapy remains widely underutilized globally and specifically in India. This gap represents a key target for intervention to save lives. Dr. Agarwal’s K99/R00 proposal aims to substantially simplify HF management by shifting the treatment paradigm for undertreated patients with HFrEF from multi-drug therapy with sequential initiation and titration to a novel late-stage implementation strategy of a HFrEF polypill of guideline-directed medical therapy including a beta-blocker, angiotensin receptor blocker, and mineralocorticoid receptor antagonist. First, Dr. Agarwal will conduct formative mixed methods research including a HF treatment consensus meeting and focus group discussions to guide development of the HFrEF polypill-based strategy in India. Second, she will evaluate whether, compared to usual care, a HFrEF polypill implementation strategy will reduce cardiovascular disease mortality and HF hospitalizations at 12 months in adults with HFrEF in India using a multi-center, type I hybrid randomized clinical trial design. She will also assess the effect of the HFrEF polypill implementation strategy on important secondary outcomes including medication adherence, markers of HF disease severity, health-related quality of life, and safety measured by adverse events. Finally, Dr. Agarwal will apply methods of process evaluation to assess implementation outcomes of the HFrEF polypill in India, a key step in translating evidence generated into broader use globally. The K99 phase will also provide essential methodological training for Dr. Agarwal to transition to research independence in the R00 phase. Dr. Agarwal proposes training in 1) implementation science methods, 2) clinical trial methods including innovative platform trial designs, and 3) regulatory science for global pharmacological clinical trials. This K99 training will prepare her to be a leading clinical trialist in global heart failure implementation science. Dr. Agarwal’s global mentorship team is led by Dr. Mark Huffman (Northwestern University, US), with key co-mentorship provided by experts in cardiovascular clinical trials in low- and middle-income countries, Drs. Dorairaj Prabhakaran (Centre for Chronic Disease Control, India) and Anushka Patel (The George Institute for Global Health, Australia). This mentorship team, supported by key collaborators (Drs. Hirschhorn, Mohanan, Ciolino) and advisors (Drs. Yancy, Lloyd-Jones), will ensure scientific success and oversee the candidate’s advanced training in their relative areas of expertise. This K99/R00 proposal supports Dr. Agarwal’s transition to launch an independent career as a future leader in global, late-stage translational cardiovascular research. Importantly, this proposal has the potential to transform HF care through simplified care in India and other settings, including in the United States.

项目摘要/摘要心力衰竭（HF）是全球领先的公共卫生问题。在低和中间的HF燃烧正在增加收入国家和临床结果仍然很差。指导指导的医疗疗法（结合不同药物类别的不同药物）提高了HF患者的发病率和死亡率减少射血分数（HFREF）。尽管有高质量的证据，但指导指导的医疗疗法在印度，在全球且尤其是全球范围内普遍存在。该差距代表了干预的关键目标挽救生命。 Agarwal博士的K99/R00提案旨在通过转变来实质性地简化HF管理通过依次主动性和滴定了一种新型的晚期实施策略，用于指导指导医疗治疗包括β受体阻滞剂，血管紧张素受体阻滞剂和盐皮质激素受体拮抗剂。首先，博士 Agarwal将进行格式混合方法研究，包括HF治疗共识会议和焦点小组讨论以指导印度HFREF Polypill战略的制定。其次，她会的评估与通常的护理相比，HFREF Polypill实施策略是否会减少心血管印度HFREF成人12个月的疾病死亡率和HF住院使用多中心I型混合随机临床试验设计。她还将评估HFREF Polypill实施的效果关于重要次要结果的策略，包括药物依从性，HF疾病严重程度的标记，与健康相关的生活质量以及通过不良事件衡量的安全性。最后，Agarwal博士将采用印度HFREF Polypill评估实施结果的过程评估，翻译的关键步骤在全球范围内生成更广泛使用的证据。 K99阶段还将提供基本的方法论培训Agarwal博士在R00阶段过渡到研究独立性。 Agarwal博士提案培训在1）实施科学方法中，2）包括创新平台试验设计在内的临床试验方法， 3）全球药物临床试验的监管科学。这种K99培训将使她成为领导者全球心力衰竭实施科学领域的临床试验者。 Agarwal博士的全球心态团队由博士领导。马克·霍夫曼（Mark Huffman）（美国西北大学），由心血管专家提供的关键会议低收入和中等收入国家的临床试验，博士。 Dorairaj Prabhakaran（慢性病中心） Control，India）和Anushka Patel（澳大利亚乔治全球健康研究所）。这支有精神的团队，由主要合作者（Mohanan，Ciolino博士）和顾问（Yancy博士，劳埃德·琼斯博士）的支持将确保科学成功，并监督候选人在其相对专业领域的高级培训。这项K99/R00提案支持Agarwal博士的过渡，以启动作为未来领导者的独立职业全球，后期翻译的心血管研究。重要的是，该提议有可能通过印度和其他环境（包括美国）的其他环境中的简化护理来转变HF护理。