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

Tatjana Welzel, Nina Schöbi, Maya C André, Douggl G N Bailey, Geraldine Blanchard-Rohner, Michael Buettcher, Serge Grazioli, Henrik Koehler, Marie-Helene Perez, Johannes Trück, Federica Vanoni, Petra Zimmermann, Andrew Atkinson, Carlos Sanchez, Elizabeth Whittaker, Saul N Faust, Julia A Bielicki, Luregn J Schlapbach, Swissped Recovery Trial, Tatjana Welzel, Nina Schöbi, Maya C André, Douggl G N Bailey, Geraldine Blanchard-Rohner, Michael Buettcher, Serge Grazioli, Henrik Koehler, Marie-Helene Perez, Johannes Trück, Federica Vanoni, Petra Zimmermann, Andrew Atkinson, Carlos Sanchez, Elizabeth Whittaker, Saul N Faust, Julia A Bielicki, Luregn J Schlapbach, 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).

Keywords: COVID-19; MIS-C; SARS-CoV-2; children; mortality; quality of life; treatment; trial.

Conflict of interest statement

AA is supported by the Swiss National Science Foundation grant CRSK-3_190977/1 and also works at Bern University Hospital. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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.

Figures

Figure 1
Figure 1
Study flow chart. PIMS-TS, Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19; IC, informed consent; GA, gestational age; mg, milligram; kg, kilogram; IV, intravenous; g, gram; w, week; m, month.
Figure 2
Figure 2
Study prodedures. PICU, Pediatric Intensive Care Unit; ED, Emergency Department; d, day; w, week; m, month. *if still hospitalized.

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