Multisystem Inflammatory Syndrome therapies in children (MISTIC): A randomized trial

Abstract

Background: Multisystem Inflammatory Syndrome in Children (MIS-C), which occurs 2-6 weeks after initial exposure to SARS-CoV-2, was first identified in early 2020 when patients presented with fever and significant inflammation, often requiring management in the intensive care unit. To date, there has been no clinical trial to determine the most effective treatment. This study compares anti-inflammatory treatments that were selected based on current treatments for Kawasaki disease, a coronary artery vasculitis that shares many clinical features with MIS-C.

Methods: This randomized, comparative effectiveness trial of children with MIS-C uses the small N Sequential Multiple Assignment Randomized Trial (snSMART) design for rare diseases to compare multiple therapies within an individual. Study participants were treated first with intravenous immunoglobulin (IVIG), and if needed, subjects were then randomized to one of three additional treatments (steroids, anakinra, or infliximab). Participants were re-randomized to remaining treatments if they did not demonstrate clinical improvement.

Conclusion: This trial continues to enroll eligible participants to determine the most effective therapies in addition to IVIG and best order in which to use them to treat MIS-C.

Trial registration: NCT04898231.

Keywords: Anakinra; IVIG, Intravenous immunoglobulin; Infliximab; Multisystem inflammatory syndrome in children (MIS-C); Randomized clinical trial; Steroids; snSMART; snSMART, small N Sequential Multiple Assignment Randomized Trial.

Fig. 1

snSMART study overview for MIS-C patients. Study drugs administered as follows: Infliximab: 10 mg/kg IV dose once; Steroids: 2 mg/kg IV divided BID (max 60 mg) with steroid taper for 2–3 weeks post-discharge; Anakinra: Up to 10 mg/kg/day (max 200 mg every 6 h) with taper and discontinuation prior to discharge. Color to be used. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Sample collection processColor to be used. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)