2/2 Kids MoD PAH Trial: Mono- vs. Duo-Therapy for Pediatric Pulmonary Arterial Hypertension-DCC

2/2 儿童国防部 PAH 试验：小儿肺动脉高压 - DCC 的单一疗法与双重疗法

基本信息

批准号：
10486005
负责人：
Hrishikesh Chakraborty
金额：
$ 91.77万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10486005
关键词：
18 year old Address Adherence Adult Age Caring Case Series Cessation of life Child Child Care Childhood Clinical Clinical Management Clinical Research Clinical Trials Clinical Trials Data Monitoring Committees Collaborations Combination Drug Therapy Combined Modality Therapy Communication Data Data Collection Data Coordinating Center Data Set Decision Making Development Diagnosis Disease Disease Progression Drug usage Early treatment Effectiveness Electronics Endothelin Receptor Antagonist Ensure Evaluation Exercise Tolerance Heart Diseases Infant Informed Consent Infrastructure Leadership Lung Lung diseases Manuscripts Measures Medicine Modernization Monitor Morbidity - disease rate Nature Newly Diagnosed Online Systems Oral Outcome Patients Pharmacotherapy Phosphodiesterase Inhibitors Preparation Protocols documentation Public Health Publications Pulmonary Heart Disease Pulmonary Hypertension Pulmonary Vascular Resistance Quality of life Randomized Randomized, Controlled Trials Reporting Reproducibility Research Institute Risk Role Safety Scheme Services Site Specialist Statistical Data Interpretation Systemic disease Testing Therapeutic Time Universities Work World Health Organization bosentan clinical care clinical practice community based participatory research data dissemination data management design efficacy evaluation electronic data capture system evidence base experience follow-up functional outcomes functional status health management hemodynamics improved inhibitor meetings mortality multidisciplinary novel novel therapeutics operation optimal treatments patient privacy phosphodiesterase V predictive modeling primary endpoint programs pulmonary arterial hypertension randomized, clinical trials right ventricular failure secondary endpoint sildenafil standard of care success targeted treatment treatment strategy web site

项目摘要

ABSTRACT Pulmonary arterial hypertension (PAH) contributes to high morbidity and mortality in children with diverse cardiopulmonary and systemic diseases. Efforts to define optimal treatment strategies for pediatric PAH have been limited by the absence of multicenter randomized controlled trials (MRCTs) and the lack of well-defined and proven endpoints for studies in children. Pediatric PAH remains understudied and relatively little is known about long-term outcomes, age-appropriate clinical endpoints and optimal therapeutic strategies for children. Drug treatment remains suboptimal as MRCTs are rare in children with PAH and current decision-making is dependent on data from adult studies or small case series in children. Based on recent success of MRCTs in establishing a new standard of care for adult PAH patients, we propose to study the potential role for initial up-front combination treatment of PAH in children consisting of two PAH-specific oral therapies that have been shown to be well- tolerated in children as monotherapies: sildenafil (a type V phosphodiesterase inhibitor) and bosentan (an endothelin receptor antagonist). Recent studies in adult PAH suggest that initiation of combined therapy with a phosphodiesterase 5 inhibitor and an endothelin receptor antagonist at the time of diagnosis, rather than sequential combination therapy, improves pulmonary hemodynamics, exercise tolerance and quality of life when compared with monotherapy. Children with PAH often require additional therapies over time in the setting of disease progression or incomplete responsiveness to monotherapy, however, there are no data regarding the potential benefits of greater and more sustained clinical improvement over time with the more aggressive combination therapy approach from the time of initial diagnosis. Studies of pediatric PAH have been further limited by the lack of well-coordinated and experienced care programs and the relative rare nature of these diseases. With the collaboration of the Pediatric Pulmonary Hypertension Network (PPHNet), a highly interactive and multidisciplinary group of academic PH programs, we propose to test the hypothesis that initiation of up-front combination therapy with sildenafil and bosentan at the time of PAH diagnosis will result in improved WHO Functional Class (FC) at 12 months in comparison with the current standard approach, which is sildenafil therapy alone. Overall, this study addresses critical gaps in pediatric PAH by testing a clinical strategy with strong potential for broad impact, and by defining useful study endpoints or novel surrogates that will facilitate evidence-based decision-making and enhance the care of children with PAH.

抽象的肺动脉高压（PAH）有助于多种多样的儿童发病率和死亡率高心肺和全身性疾病。为儿科PAH定义最佳治疗策略的努力已由于缺乏多中心随机对照试验（MRCT）而受到限制，并且缺乏定义明确的和经过验证的儿童研究终点。小儿PAH仍在研究中，对长期结局，适合年龄的临床终点和儿童的最佳治疗策略。药品治疗仍然是最佳的，因为PAH儿童中的MRCT很少，并且目前的决策取决于关于儿童的成人研究或小病例系列的数据。基于MRCT在建立一个成人PAH患者的新护理标准，我们建议研究初始组合的潜在作用 PAH在包括两种PAH特异性口服疗法组成的儿童中的治疗在儿童中耐受为单疗法：西地那非（一种V型磷酸二酯酶抑制剂）和波森坦（一个内皮素受体拮抗剂）。对成人PAH的最新研究表明，与磷酸二酯酶5抑制剂和诊断时内皮素受体拮抗剂，而不是顺序组合疗法，改善肺血液动力学，运动耐受性和生活质量时与单一疗法相比。患有PAH的孩子通常需要随着时间的流逝需要额外的疗法疾病进展或对单一疗法的反应性不完全，没有有关随着时间的流逝，更大和持续的临床改进的潜在好处，更具侵略性联合疗法方法从初始诊断之日起。小儿PAH的研究进一步受到缺乏协调和经验丰富的护理计划的限制以及这些相对罕见的本质疾病。通过小儿肺动脉高压网络（PPHNET）的合作，高度互动和多学科的学术pH计划小组，我们建议检验以下假设在诊断时，与西地那非和波森坦的前期组合疗法将导致与当前标准方法相比，在12个月时改进了WHO职能类（FC）这是西地那非治疗。总体而言，这项研究通过测试临床来解决小儿PAH的关键差距具有强大影响力的策略，并通过定义有用的研究终点或新型替代物促进基于证据的决策并增强PAH儿童的护理。