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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：
10214114
负责人：
Hrishikesh Chakraborty
金额：
$ 93.54万
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/10214114
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 Endothelin Receptor Antagonist Ensure Evaluation Exercise Tolerance Heart Diseases Heart failure 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 Clinical Trials 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 base 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/antagonist meetings mortality multidisciplinary novel novel therapeutics operation optimal treatments patient privacy phosphodiesterase V predictive modeling primary endpoint programs pulmonary arterial hypertension 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.

摘要