PITCH HF (DCC)

音高 HF (DCC)

基本信息

批准号：
8294128
负责人：
SUSAN FERA ASSMANN
金额：
$ 103.71万
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 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8294128
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）：PIDD-HF将是评估选择性肺血管扩张剂的作用，即5型磷酸二酯酶（PDE5）抑制剂tadalafil对长期临床结局（左心室（LV）心脏失调（LV）心脏功能障碍（LVSD（LVSD）和第二个phs phs phs phs）和第二个phormenary phormenary phormenary phormonary phronary phormenary phormenary tadalafil的长期临床结局。 LVSD继发性pH和右心室（RV）功能障碍的患者构成了HF的高风险亚群，发病率和死亡率增加。但是，目前的基于准则的治疗重点是LV功能障碍的治疗。对该人群中PDE5抑制的安慰剂对照研究表明，运动能力和生活质量的预后标志有所改善，并为达拉非利对HF发病率和死亡率的影响的多中心试验提供了基础。三个目的地址：（1）到达主要终点（心血管（CV）死亡率或HF住院）和次要终点（时间为CV死亡率，HF住院，全因死亡率； CV/HF住院频率）；（2）功能能力（步行6分钟步行距离）和生活质量（明尼苏达州与HF问卷生活）的变化，从基线到3个月至3个月；（3）建立血浆样品存储库（基线，3，18个月），用于对潜在生物标志物的辅助研究，这些研究可能预测了对PDE5抑制的有益反应。 CCC（马萨诸塞州综合医院，PI：MARC SEMIGRAN MD）和DCC（新英格兰研究机构，PIS：Rebecca Li PhD； Susan Assmann Phd）提供广泛的补充专业知识和经验，以确保试验成功。研究药物的价值为[5400万美元]，以及对药物配送中心的支持，将由[Eli Lilly Inc.]作为KID礼物提供，在1年级招募100个认证地点（美国和加拿大），Pitch-HF将在2 - 4年内招募2,102名受试者，并在2 - 4年内招募2,102名受试者，并接受2。5年的治疗。 [在选定地点进行的一项试点研究中已证明了可行性。该试验将具有85个地点承诺。主要分析将使用COX回归模型并适当地分析协方差。提出了三个临时分析。患者群体包括：成人E21年；具有LVSD的NYHA II-IV HF（LVEF <40％）；要么是：在12个月内发作的HF发作或血浆BNP水平E300 pg/mL或NT-Probnp E1800PG/ml的发作，在3个月内测量。所有患者都必须在6个月内记录了次要pH，并进行了基于指南的医疗疗法。非裔美国人不耐等异形外二硝酸盐/氢嗪治疗。该开创性试验的结果（如果为阳性）将提供一种新的，有效的治疗，从而实质性的HF患者具有较高的发病率和死亡率。如果阴性，它将阻止在收缩期HF中使用PDE5抑制剂，并会激发对HF患者RV功能障碍的其他潜在疗法的进一步研究。