A multicenter trial to test pitavastatin calcium in youth with combined dyslipidemia of obesity: Design, implementation, challenges, and responses

Sarah D. de Ferranti, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115. Electronic address: Sarah.deferranti@cardio.chboston.org.
Jessica E. Teng, Carelon Research, Newton, MA 55 Chapel Street, Suite 105, Newton, MA 02458.
Silva A. Arslanian, Faculty Pavilion-Lawrenceville, Room 6102 University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh 4401 Penn Ave. Pittsburgh, PA 15224-1334.
Andrew M. Atz, Medical University of South Carolina, Charleston SC.
Julie A. Brothers, Children's Hospital of Philadelphia, Philadelphia, PA.
Mark J. Cartoski, Nemours Children's Health, 1600 Rockland Road, Wilmington, DE 19803.
D'Andrea R. Freemon, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD.
Sheela N. Magge, Johns Hopkins University School of Medicine, Baltimore, MD.
William T. Mahle, Children's Healthcare of Atlanta Cardiology, 2220 North Druid Hills Road NE Atlanta, GA 30329.
Michele Mietus-Snyder, Children's National Hospital, 111 Michigan Ave NW, Washington DC, 20003 George Washington University School of Medicine and Health Sciences, Washington DC.
Amy Peterson, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Geetha Raghuveer, Children's Mercy Hospital, University of Missouri Kansas City School of Medicine, Kansas City, MO.
Mark W. Russell, CS Mott Children's Hospital, University of Michigan, Ann Arbor, MI.
Amy S. Shah, Cincinnati Children's Hospital Medical Center & The University of Cincinnati.
Craig A. Sponseller, Kowa Pharmaceuticals America, Inc., Montgomery, AL.
Mario Stylianou, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD.
Felicia L. Trachetenberg, Carelon Research, Newton, MA 55 Chapel Street, Suite 105, Newton, MA 02458.
Elaine M. Urbina, University of Cincinnati College of Medicine 3333 Burnet Ave, Cincinnati, OH 45229.
Adam L. Ware, University of Utah, Salt Lake City, UT.
Justin Zachariah, Texas Children's Hospital, Baylor College of Medicine, 17600 Interstate 45 South Texas Children's Hospital The Woodlands, TX 77384.
Varsha V. Zadokar, Nemours Children's Health, 1600 Rockland Road, Wilmington, DE 19803.
Brian W. McCrindle, 555 University Avenue, Division of Cardiology/Labatt Heart Centre, The Hospital for Sick Children Toronto, Ontario Canada M5G 1×8.

Document Type

Journal Article

Publication Date

12-15-2025

Journal

American heart journal

DOI

10.1016/j.ahj.2025.107327

Keywords

adolescent; carotid intimal-medial thickness; child; cholesterol; dyslipidemia; obesity; pulse wave velocity

Abstract

BACKGROUND: Combined dyslipidemia of obesity (CDO) is a prevalent atherogenic lipid disorder characterized by high TG, low HDL, high non-HDL, and a preponderance of small LDL particles. Lifestyle modification is the mainstay of treatment but is often insufficient; a pharmacologic approach could augment care but has not been rigorously evaluated. METHODS: The Dyslipidemia of Obesity Intervention in Teens (DO IT!) Trial was a two-year randomized controlled double-blind study designed to measure the effect and safety profile of pitavastatin calcium vs. placebo on vascular measures of early atherosclerosis, and standard and advanced lipid profiles in children and adolescents with CDO. We present the rationale, design, and study procedures, and share challenges, responses, and lessons learned. RESULTS: Participants were recruited from 17 sites; goal 177, with 122 consented (68.9%). Facilitators to recruitment included familiarity of site investigators with CDO management, relationship with local obesity programs, and study incentives. Barriers included two-year study duration, number of study visits, and COVID-19 pandemic effects. The research team added recruitment sites, expanded eligibility, shared educational and promotional materials, and bolstered site engagement but enrollment was insufficient, and the trial was stopped early. CONCLUSIONS: The DO IT! Trial was the first to evaluate effects of pitavastatin vs. placebo on vascular measures, lipid outcomes and potential adverse effects. Recruitment challenges limited the study sample, but findings may still inform cardiovascular prevention. Future studies are more likely to be more successful with early patient-family input, shorter study duration, and fewer study visits integrated with clinical care close to home.

Department

Pediatrics

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