TY - JOUR
T1 - Kids Mod PAH trial
T2 - A multicenter trial comparing mono- versus duo-therapy for initial treatment of pediatric pulmonary hypertension
AU - Collaco, Joseph M.
AU - Abman, Steven H.
AU - Austin, Eric D.
AU - Avitabile, Catherine M.
AU - Bates, Angela
AU - Fineman, Jeffrey R.
AU - Freire, Grace A.
AU - Handler, Stephanie S.
AU - Ivy, Dunbar D.
AU - Krishnan, Usha S.
AU - Mullen, Mary P.
AU - Varghese, Nidhy P.
AU - Yung, Delphine
AU - Nies, Melanie K.
AU - Everett, Allen D.
AU - Zimmerman, Kanecia O.
AU - Simmons, William
AU - Chakraborty, Hrishikesh
AU - Yenokyan, Gayane
AU - Newell-Sturdivant, Allison
AU - Christensen, Eric
AU - Eyzaguirre, Lindsay M.
AU - Hanley, Daniel F.
AU - Rosenzweig, Erika B.
AU - Romer, Lewis H.
N1 - Publisher Copyright:
© 2023 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - bosentan
KW - children
KW - multicenter randomized control trial
KW - pulmonary arterial hypertension
KW - sildenafil
UR - http://www.scopus.com/inward/record.url?scp=85175630535&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85175630535&partnerID=8YFLogxK
U2 - 10.1002/pul2.12305
DO - 10.1002/pul2.12305
M3 - Article
C2 - 37915400
AN - SCOPUS:85175630535
SN - 2045-8932
VL - 13
JO - Pulmonary Circulation
JF - Pulmonary Circulation
IS - 4
M1 - e12305
ER -