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

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 2-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 2-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.

Clinicaltrials: gov identifier: NCT02956590.