Joseph M. Collaco, Steven H. Abman, Eric D. Austin, Catherine M. Avitabile, Angela Bates, Jeffrey R. Fineman, Grace A. Freire, Stephanie S. Handler, Dunbar D. Ivy, Usha S. Krishnan, Mary P. Mullen, Nidhy P. Varghese, Delphine Yung, Melanie K. Nies, Allen D. Everett, Kanecia O. Zimmerman, William Simmons, Hrishikesh Chakraborty, Gayane Yenokyan, Allison Newell‐Sturdivant, Eric Christensen, Lindsay M. Eyzaguirre, Daniel F. Hanley, Erika B. Rosenzweig, Lewis H. Romer
Johns Hopkins University School of Medicine. Children’s Hospital Colorado. Vanderbilt University Medical Center. Children’s Hospital of Philadelphia. University of California San Francisco. Johns Hopkins All Children’s Hospital. Medical College of Wisconsin. Vagelos College of Physicians and Surgeons Columbia University. Boston Children’s Hospital. Baylor College of Medicine and Texas Children’s Hospital. University of Washington School of Medicine. Duke University.
United States
Pulmonary Circulation
Pulm Circ 2023; 13:
DOI: 10.1002/pul2.12305
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.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes