Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial

Abstract

Introduction: In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG.; Methods and Analysis: Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned.; Significance: Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments.; Ethics and Dissemination: The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362).; Registration Details: The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT04826588). (Copyright © 2022 Welzel, Schöbi, André, Bailey, Blanchard-Rohner, Buettcher, Grazioli, Koehler, Perez, Trück, Vanoni, Zimmermann, Atkinson, Sanchez, Whittaker, Faust, Bielicki, Schlapbach and the Swissped Recovery Trial.)eCollection. Cited Medium: Print. NLM ISO Abbr: Front Pediatr. PubMed Central ID: PMC9163685. Linked References: J Biomed Inform. 2009 Apr;42(2):377-81. (PMID: 18929686); Rheumatology (Oxford). 2019 Apr 1;58(4):672-682. (PMID: 30535127); N Engl J Med. 2021 Jul 1;385(1):11-22. (PMID: 34133854); Lancet. 2020 May 23;395(10237):1607-1608. (PMID: 32386565); N Engl J Med. 2020 Jul 23;383(4):393-395. (PMID: 32598829); Circulation. 2017 Apr 25;135(17):e927-e999. (PMID: 28356445); Int J Clin Pract. 2021 Sep;75(9):e14471. (PMID: 34107136); Intensive Care Med. 2021 Jan;47(1):90-93. (PMID: 33057783); J Exp Med. 2021 Jun 7;218(6):. (PMID: 33904890); JAMA. 2020 Jul 21;324(3):259-269. (PMID: 32511692); N Engl J Med. 2020 Jul 23;383(4):334-346. (PMID: 32598831); Eur Child Adolesc Psychiatry. 2004;13 Suppl 2:II47-54. (PMID: 15243786); BMJ Open. 2015 Sep 18;5(9):e008522. (PMID: 26384724); Nat Med. 2022 Jan;28(1):193-200. (PMID: 34931076); Front Pediatr. 2021 May 26;9:667507. (PMID: 34123970); JAMA. 2021 Mar 2;325(9):855-864. (PMID: 33523115); Ital J Pediatr. 2021 Feb 8;47(1):24. (PMID: 33557873); JAMA. 2021 Mar 16;325(11):1074-1087. (PMID: 33625505); Nat Med. 2020 Nov;26(11):1701-1707. (PMID: 32812012); BMC Pediatr. 2021 Nov 18;21(1):516. (PMID: 34794410); Arthritis Rheumatol. 2021 Apr;73(4):e13-e29. (PMID: 33277976). Linking ISSN: 22962360. Subset: PubMed not MEDLINE; Date of Electronic Publication: 2022 May 20. ; Original Imprints: Publication: Lausanne : Frontiers Media SA, [2013]- <br />