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Published on: May 11, 2015
Kids Mod PAH trial: A multicenter trial comparing mono- versus duo-therapy for initial treatment of pediatric
Joseph M Collaco1, Steven H Abman2, Eric D Austin3
1Departments of Pediatrics, Neurology, Anesthesiology and Critical Care Medicine, and Biostatistics Johns Hopkins University School of Medicine Baltimore Maryland USA.
Insights
This study investigates if upfront combination therapy improves outcomes for pediatric pulmonary hypertension (PH). The Kids Mod PAH Trial compares sildenafil plus bosentan versus sildenafil alone to assess treatment effectiveness in children.
Area of Science:
- Pediatric Cardiology
- Pulmonary Medicine
- Clinical Trials
Background:
- Pediatric pulmonary hypertension (PH) significantly increases morbidity and mortality.
- Lack of quality endpoints and robust clinical trial data hinder PH care advances in children.
- Adult studies show benefits of upfront combination therapy, but pediatric data is lacking.
Purpose of the Study:
- To evaluate if upfront combination therapy (sildenafil and bosentan) improves PH outcomes in children compared to sildenafil alone.
- To address the efficacy of combination therapy in various pediatric PH categories.
- To establish a robust infrastructure for future pediatric PH clinical trials.
Main Methods:
- A multicenter Phase III trial (Kids Mod PAH Trial) was designed.
- Participants receive either sildenafil and bosentan or sildenafil alone.
- Primary endpoint is WHO functional class at 12 months; secondary and exploratory endpoints include clinical worsening, echocardiography, 6-minute walk distance, NT-proBNP, biomarkers, actigraphy, and quality of life.
Main Results:
- This section describes the inception and design of the Kids Mod PAH Trial.
- The study aims to address critical gaps in pediatric PH pharmacologic therapy.
- Results are pending the trial's completion.
Conclusions:
- The Kids Mod PAH Trial is crucial for advancing evidence-based care for pediatric pulmonary hypertension.
- Establishing a PPHNet Clinical Trials Network will facilitate future research.
- Findings will guide pharmacologic therapies for children with PH.
Abstract:
Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network.
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