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

• 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
• 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

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)是全球主要的公共卫生问题。中低海拔地区高铁负荷呈上升趋势。 收入国家和临床结果仍然很差。指导方针的医疗治疗(组合 不同药物类别的不同药物)可改善心力衰竭患者的发病率和死亡率 降低射血分数(HFrEF)。尽管有这些高质量的证据，指导方针的药物治疗 在全球范围内，特别是在印度，仍然普遍未得到充分利用。这一差距是干预的关键目标 为了拯救生命。Agarwal博士的K99/R00提案旨在通过将 多药序贯治疗HFrEF患者的治疗模式 一种新的指导药物治疗的HFrEF聚丸后期实施策略的滴定 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，戴维斯博士。 Agarwal将进行形成性混合方法研究，包括HF治疗共识会议和 焦点小组讨论，以指导HFrEF Polypill在印度的战略发展。第二，她会 评估与常规护理相比，HFrEF息肉的实施策略是否会减少心血管疾病 印度I型多中心HFrEF成人患者12个月的疾病死亡率和心力衰竭住院情况 混合随机临床试验设计。她还将评估HFrEF Polypill实施的效果 关于重要的次要结果的策略，包括服药依从性、心力衰竭严重程度的标志物、 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，阿加瓦尔博士将运用 评估HFrEF聚合体在印度的实施结果的过程评估，这是翻译的关键步骤 产生的证据在全球范围内得到更广泛的使用。K99阶段还将提供基本的方法 对Agarwal博士进行培训，使其在R00阶段过渡到研究独立。阿加瓦尔博士建议进行培训 1)实施科学方法，2)临床试验方法，包括创新的平台试验设计，以及 3)全球药理学临床试验的调控科学。这次K99培训将为她成为一名领军人物做好准备 全球心力衰竭实施科学临床试验专家。阿加瓦尔博士的全球指导团队由阿加沃博士领导。 Mark Huffman(美国西北大学)，心血管专家提供关键共同指导 低收入和中等收入国家的临床试验，Dorairaj Prabhakaran博士(慢性病中心 印度)和阿努什卡·帕特尔(澳大利亚乔治全球卫生研究所)。这个导师团队， 得到主要合作者(赫希霍恩博士、莫哈南博士、乔利诺博士)和顾问(扬西博士、劳埃德-琼斯博士)的支持， 将确保科学上的成功，并监督候选人在其相关专业领域的高级培训。 这份K99/R00提案支持阿加瓦尔博士过渡到作为未来的领导者开始独立的职业生涯 全球性的晚期转化性心血管研究。重要的是，这项提议有可能 在印度和包括美国在内的其他环境中，通过简化护理来改变心力衰竭的护理。