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

doi:10.3389/fped.2022.905046

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

Front Pediatr. 2022 May 20:10:905046. doi: 10.3389/fped.2022.905046. eCollection 2022.

Authors

Tatjana Welzel^{1

2

3}, Nina Schöbi⁴, Maya C André^{5

6}, Douggl G N Bailey⁷, Geraldine Blanchard-Rohner⁸, Michael Buettcher^{2

9}, Serge Grazioli¹⁰, Henrik Koehler¹¹, Marie-Helene Perez¹², Johannes Trück¹³, Federica Vanoni^{14

15}, Petra Zimmermann^{16

17

18}, Andrew Atkinson¹, Carlos Sanchez¹, Elizabeth Whittaker^{19

20}, Saul N Faust^{21

22}, Julia A Bielicki^{1

23}, Luregn J Schlapbach^{24

25}; Swissped Recovery Trial

Affiliations

¹ Paediatric Research Center, University Children's Hospital Basel, University of Basel, Basel, Switzerland.
² Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland.
³ Division of Paediatric Rheumatology, University Children's Hospital Basel, University of Basel, Basel, Switzerland.
⁴ Division of Paediatric Infectious Diseases, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Division of Respiratory and Critical Care Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland.
⁶ Department of Paediatric Hematology and Oncology, University Children's Hospital, Eberhard Karls University, Tuebingen, Germany.
⁷ Paediatric and Neonatal Intensive Care Unit, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
⁸ Paediatric Immunology and Vaccinology Unit, Division of General Paediatrics, Department of Child, Woman and Adolescent Medicine, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
⁹ Paediatric Infectious Diseases Unit, Department of Paediatrics, Cantonal Hospital Lucerne, Lucerne, Switzerland.
¹⁰ Division of Neonatal and Paediatric Intensive Care, Department of Child, Woman and, Adolescent Medicine, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
¹¹ Department of Paediatrics, Cantonal Hospital Aarau, Aarau, Switzerland.
¹² Paediatric Intensive Care Unit, University Hospital Lausanne, Lausanne, Switzerland.
¹³ Division of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich (UZH), Zurich, Switzerland.
¹⁴ Clinic of Paediatrics, Paediatric Institute of Southern Switzerland, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland.
¹⁵ Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland.
¹⁶ Department of Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
¹⁷ Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland.
¹⁸ Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
¹⁹ Section of Paediatric Infectious Diseases, Imperial College London, London, United Kingdom.
²⁰ Department of Paediatric Infectious Diseases, Imperial College Healthcare NHS Trust, London, United Kingdom.
²¹ NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
²² Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
²³ Centre for Neonatal and Paediatric Infection, St George's University, London, United Kingdom.
²⁴ Department of Intensive Care and Neonatology, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
²⁵ Paediatric Intensive Care Unit, Queensland Children's Hospital and Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia.

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.

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.

Associated data

ClinicalTrials.gov/NCT04826588