PITCH HF (DCC)

音高 HF (DCC)

基本信息

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
项目类别：
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

项目摘要

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）对左心衰竭 (HF) 患者长期临床结果影响的试验。心室（LV）收缩功能障碍（LVSD）和继发性肺动脉高压（PH）。继发性 PH 和右心室 (RV) 功能障碍的 LVSD 患者构成心力衰竭的高危亚群，其发病率和死亡率较高。然而，目前基于指南的治疗侧重于左室功能障碍的治疗。在该人群中抑制 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影响的多中心试验提供了基础。三个目标涉及：(1) 达到主要终点（心血管（CV）死亡率或心力衰竭住院）的时间和次要终点（心血管（CV）死亡率、心力衰竭住院、全因死亡率的时间；以及心血管/心力衰竭住院频率）； (2) 从基线到 3 个月和 18 个月的功能能力（6 分钟步行距离）和生活质量（明尼苏达心力衰竭生活问卷）的变化； (3) 建立血浆样本库（基线、3、18 个月），用于潜在生物标志物的辅助研究，这些生物标志物可以预测对 PDE5 抑制的有益反应。 CCC（马萨诸塞州总医院，PI：Marc Semigran MD）和 DCC（新英格兰研究所，PI：Rebecca Li 博士；Susan Assmann 博士）提供广泛的互补专业知识和经验，以确保试验成功。价值 [5400 万美元] 的研究药物以及对药物分销中心的支持将由 [Eli Lilly Inc.] 作为儿童礼物提供在 PITCH 第一年招募 100 个认证中心（美国和加拿大） -HF 将在第 2-4 年招募 2,102 名受试者，并对他们进行平均 2.5 年的治疗跟踪。 [在选定地点进行的试点研究已证明了可行性。迄今为止已获得 82 个站点承诺。] 该试验将有 85% 的功效检测到主要结局的 2.5 年发生率相对降低 20%（从 30% 降至 24%），且 a = 0.05 且受试者流失税率高达15%。主要分析将是意向性治疗，酌情使用 Cox 回归模型和协方差分析。提出了三项中期分析。患者群体包括： 21 岁以上的成年人； NYHA II-IV 级心力衰竭，伴有 LVSD（LVEF < 40%）；以及：12 个月内发生失代偿性心力衰竭，或 3 个月内测得血浆 BNP 水平 e300 pg/ml 或 NT-proBNP e1800pg/ml。所有患者必须在 6 个月内记录继发性 PH，并接受稳定的基于指南的药物治疗。不耐受二硝酸异山梨酯/肼屈嗪联合疗法的非裔美国人可以入组。这项开创性试验的结果如果是积极的，将为大量发病率和死亡率较高的心力衰竭患者提供一种新的、有效的治疗方法。如果结果为阴性，将阻止 PDE5 抑制剂在收缩性心力衰竭中的使用，并将激发对心力衰竭患者右心室功能障碍的其他潜在疗法的进一步研究。