PITCH HF (DCC)

音高 HF (DCC)

• 批准号: 8459908
• 负责人: SUSAN FERA ASSMANN
• 金额: $ 188.04万
• 依托单位: NEW ENGLAND RESEARCH INSTITUTES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459908
• 关键词: Activities of Daily Living; Address; Adult; African American; Ancillary Study; Annual Reports; Biological Markers; Boston; Canada; Cardiovascular system; Case Report Form; Cessation of life; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Code; Consent Forms; Contractor; Contracts; Country; Cyclic GMP; Data; Data Coordinating Center; Databases; Doctor of Philosophy; Documentation; Double-Blind Method; Drug Labeling; EFRAC; Enrollment; Ensure; Equipment and supply inventories; Erectile dysfunction; Europe; Event; Exercise; FDA approved; Frequencies; Functional disorder; Funding; General Hospitals; Gifts; Goals; Guidelines; Health; Heart failure; Hospitalization; Hospitals; Hydralazine; Intention; Investigation; Isosorbide Dinitrate; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Life; Lung; Manuals; Manuscripts; Massachusetts; Measures; Medical; Minnesota; Modeling; Monitor; Morbidity - disease rate; Multicenter Trials; NT-proBNP; New England; North America; Oral; Outcome; Patients; Pattern; Pharmaceutical Preparations; Pilot Projects; Placebos; Plasma; Population; Preparation; Procedures; Prognostic Marker; Protocols documentation; Pulmonary Hypertension; Pulmonary artery structure; Qualifying; Quality of life; Questionnaires; Randomized; Recruitment Activity; Relative (related person); Reporting; Research; Research Institute; Rest; Right Ventricular Dysfunction; Risk; Safety; Sampling; Seminal; Signal Transduction; Site; Specimen; Statistical Data Interpretation; Surveys; Symptoms; System; Systolic Pressure; Systolic heart failure; Testing; Time; Training; Validation; Vasodilator Agents; Ventricular; Walking; Woman; Work; base; data management; drug distribution; effective therapy; experience; high risk; inhibitor/antagonist; mortality; outcome forecast; patient population; payment; phosphodiesterase V; phosphoric diester hydrolase; placebo controlled study; pressure; primary outcome; programs; pulmonary arterial hypertension; repository; response; success; tadalafil; web site

DESCRIPTION (provided by applicant): PITCH-HF will be the first trial to assess the effect of a selective pulmonary vasodilator, the type 5 phosphodiesterase (PDE5) inhibitor tadalafil, on long-term clinical outcomes in heart failure (HF) patients with left ventricular (LV) systolic dysfunction (LVSD) and secondary pulmonary hypertension (PH). LVSD patients with secondary PH and right ventricular (RV) dysfunction constitute a high-risk subpopulation of HF with increased morbidity and mortality. However, current guideline-based therapy focuses on the treatment of LV dysfunction. Placebo-controlled studies of PDE5 inhibition in this population have demonstrated improvements in the prognostic markers of exercise capacity and quality of life and provide the basis for a multicenter trial of the effect of tadalafil on HF morbidity and mortality. Three Aims address: (1) Time to the primary endpoint (cardiovascular (CV) mortality or HF hospitalization) and secondary endpoints (time to CV mortality, HF hospitalization, all-cause mortality; and frequency of CV/HF hospitalizations); (2) Changes in functional capacity (6-minute walk distance) and quality of life (Minnesota Living with HF questionnaire), from baseline to 3 and 18 months; and (3) Establishment of a plasma samples repository (baseline, 3, 18 months) for ancillary studies of potential biomarkers that may predict beneficial responses to PDE5 inhibition. The CCC (Massachusetts General Hospital, PI: Marc Semigran MD) and the DCC (New England Research Institutes, PIs: Rebecca Li PhD; Susan Assmann PhD) provide extensive complementary expertise and experience to ensure trial success. Study drug, valued at [$54 million], as well as support for the Drug Distribution Center, will be provided as an in-kid gift by [Eli Lilly Inc.] Recruiting 100 certified sites (US and Canada) in year 1, PITCH-HF will enroll 2,102 subjects in years 2-4 and follow them for an average of 2.5 years of treatment. [Feasibility has been demonstrated in a pilot study conducted at selected sites. 82 site commitments have been obtained to-date.] The trial will have 85% power to detect a 20% relative reduction in the 2.5-year rate for the primary outcome (from 30% to 24%) with a = 0.05 and subject attrition rates of up to 15%. Primary analyses will be intention-to-treat, using Cox regression models and analysis of covariance as appropriate. Three interim analyses are proposed. The patient population includes: Adults e21 years; NYHA Class II-IV HF with LVSD (LVEF < 40%); and either: an episode of decompensated HF within 12 months, or plasma BNP level e300 pg/ml or NT-proBNP e1800pg/ml measured within 3 months. All patients must have documented secondary PH within 6 months, and be on stable guideline-based medical therapy. African-Americans intolerant of combined isosorbide dinitrate/hydralazine therapy may be enrolled. The results of this seminal trial, if positive, will provide a new, effective therapy fo a substantive segment of HF patients that has a high morbidity and mortality. If negative, it will deter the use of PDE5 inhibitors in systolic HF and will motivate further investigation into other potential therapies for RV dysfunction in HF patients.

描述(由申请人提供)：Pitch-HF将是第一个评估选择性肺血管扩张剂--5型磷酸二酯酶(PDE5)抑制剂他达拉非对心力衰竭(HF)、左心室(LV)收缩功能障碍(LVSD)和继发性肺动脉高压(PH)患者的长期临床结果的影响的试验。继发性肺动脉高压和右室功能不全的LVSD患者是心力衰竭的高危人群，发病率和死亡率增加。然而，目前基于指南的治疗主要集中在左心功能不全的治疗上。在这一人群中进行的抑制PDE5的安慰剂对照研究表明，运动能力和生活质量的预后指标有所改善，并为他达拉非对心力衰竭发病率和死亡率的影响进行多中心试验提供了基础。三个目标涉及：(1)到达主要终点(心血管(CV)死亡率或HF住院)和次要终点(CV死亡率、HF住院时间、全原因死亡率；以及CV/HF住院频率)的时间；(2)功能容量(6分钟步行距离)和生活质量(明尼苏达州接受HF问卷调查)的变化，从基线到3个月和18个月；以及(3)建立血浆样本库(基线，3个月，18个月)，用于可能预测对PDE5抑制的有益反应的潜在生物标志物的辅助研究。CCC(麻省总医院，PI：Marc Semgran MD)和DCC(新英格兰研究院，PI：Rebecca Li Phd；Susan Assmann PhD)提供广泛的互补专业知识和经验，以确保试验成功。研究药物，价值[5400万美元]，以及对药物分销中心的支持，将由[礼来公司]作为儿童礼物提供。Pitch-HF在第一年招募了100个经过认证的地点(美国和加拿大)，将在第二到第四年招募2102名受试者，并对他们进行平均2.5年的治疗。[在选定地点进行的试点研究证明了可行性。迄今已获得82项现场承诺。]该试验将有85%的权力来检测主要结果的2.5年相对下降20%(从30%到24%)，a=0.05，受试者流失率高达15%。主要分析将使用COX回归模型和适当的协方差分析进行意向治疗。本文提出了三项中期分析。患者群体包括：21岁的成年人；NYHA II-IV级心衰伴左室缺如(LVEF&lt；40%)；或者：12个月内发生失代偿性心衰，或3个月内测量血浆BNP水平e300pg/ml或NT-proBNP e1800pg/ml。所有患者必须在6个月内记录继发性肺高压，并接受稳定的基于指南的药物治疗。对硝酸异山梨酯/肼丙嗪联合疗法不耐受的非裔美国人可以参加试验。这项开创性试验的结果如果呈阳性，将为发病率和死亡率高的实质性心力衰竭患者提供一种新的、有效的治疗方法。如果阴性，它将阻止PDE5抑制剂在收缩心衰中的使用，并将推动进一步研究其他治疗心力衰竭患者右室功能障碍的潜在疗法。