Randomised Evaluation of COVID-19 Therapy (RECOVERY) in Children With PIMS-TS in Switzerland (SWISSPED-RECOVERY)

NCT04826588 | Completed Phase 3 DMC

• 1 other identifier: 2021-00362; ks21Bielicki2
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 10

Brief Summary

The study is to provide reliable estimates of the effect of study treatment on hospital length of stay through to 28 days after randomisation. The protocol describes an overarching trial design to provide reliable evidence on the efficacy of candidate therapies for children hospitalised with PIMS-TS. It is an adaptive pragmatic platform trial with an open-label randomisation. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated.

Conditions

Paediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS)

Keywords

coronavirus-disease (COVID-19); SARS coronavirus 2 (SARS-CoV-2); tocilizumab; anakinra; Human normal immunoglobulin (IVIg); Methylprednisolone sodium succinate

Outcome Measures

Primary Outcomes (1)

• Hospital length of stay

  effect of study treatment on hospital length of stay

  Within 28 days after randomisation

Secondary Outcomes (2)

• All-cause mortality among patients

  Within 28 days and up to 6 months after randomisation

• Composite endpoint of death or need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

  Within 28 days and up to 6 months after randomisation

Other Outcomes (7)

• Need for (and duration of) ventilation

  Within 28 days and up to 6 months after randomisation

• Need for renal replacement therapy

  Within 28 days and up to 6 months after randomisation

• Number of patients who had thrombotic events

  Within 28 days and up to 6 months after randomisation

Study Arms (2)

Methylprednisolone sodium succinate 10 mg/kg

ACTIVE COMPARATOR

Methylprednisolone sodium succinate 10 mg/kg intravenously once daily for 3 days (max 1 g per dose)

Drug: Methylprednisolone sodium succinate 10 mg/kg intravenously

Human normal immunoglobulin (IVIg)

ACTIVE COMPARATOR

Human normal immunoglobulin (IVIg) 2g/kg intravenously as a single dose in line with guidance for dosing and administration in Kawasaki disease

Biological: Human normal immunoglobulin (IVIg)

Interventions

Methylprednisolone sodium succinate 10 mg/kg intravenously DRUG

Methylprednisolone sodium succinate 10 mg/kg intravenously once daily for 3 days (max 1 g per dose)

Methylprednisolone sodium succinate 10 mg/kg

Human normal immunoglobulin (IVIg) BIOLOGICAL

Human normal immunoglobulin (IVIg) 2g/kg intravenously as a single dose in line with guidance for dosing and administration in Kawasaki disease

Human normal immunoglobulin (IVIg)

Eligibility Criteria

• Age: 44 Weeks - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Hospitalised children (aged \<18 years old)
• SARS-CoV-2 infection associated disease (clinically suspected or laboratory confirmed) with evidence of single or multi-organ dysfunction (called Pediatric Multisystem Inflammatory Syndrome temporally associated with COVID-19 \[PIMS-TS\]).
• No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial

You may not qualify if:

• Neonates/infants with a corrected gestational age of \<= 44 weeks
• If the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms or that the patient should definitely be receiving one of the active drug treatment arms, then that arm will not be available for randomisation for that patient.

Sponsors & Collaborators

• University Children's Hospital Basel: lead
• SwissPedNet: collaborator

Study Sites (10)

Cantonal Hospital Aarau, Department of Paediatrics

Aarau, 5001, Switzerland

Location

University of Basel Children's Hospital

Basel, 4056, Switzerland

Location

Ente Ospedaliero Cantonale Ticino (EOC) Pediatrica

Bellinzona, 6500, Switzerland

Location

Department of Pediatrics, University of Bern

Bern, 3010, Switzerland

Location

Department of Child, Woman and, Adolescent Medecine, Geneva University Hospitals and Faculty of Medicine

Geneva, Switzerland

Location

Department of Pediatrics,University Hospital of Lausanne (CHUV)

Lausanne, Switzerland

Location

Department of Pediatrics, Cantonal Hospital Luzern

Lucerne, 6000, Switzerland

Location

Children's Hospital of Eastern Switzerland

Sankt Gallen, 9006, Switzerland

Location

Department of Pediatrics, Cantonal Hospital Fribourg

Villars-sur-Glâne, 1752, Switzerland

Location

University Children's Hospital Zuerich

Zurich, 8032, Switzerland

Location

Related Publications (5)

• Welzel T, Atkinson A, Schobi N, Andre MC, Bailey DGN, Blanchard-Rohner G, Buettcher M, Grazioli S, Koehler H, Perez MH, Truck J, Vanoni F, Zimmermann P, Sanchez C, Bielicki JA, Schlapbach LJ; Swissped RECOVERY Trial Group. Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial. Lancet Child Adolesc Health. 2023 Apr;7(4):238-248. doi: 10.1016/S2352-4642(23)00020-2. Epub 2023 Feb 3.

  PMID: 36746174 RESULT

• Schobi N, Sanchez C, Welzel T, Bamford A, Webb K, Rojo P, Tremoulet A, Atkinson A, Schlapbach LJ, Bielicki JA; Swissped-RECOVERY trial group. Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland. BMJ Open. 2024 Apr 25;14(4):e078137. doi: 10.1136/bmjopen-2023-078137.

  PMID: 38670610 DERIVED

• Andre MC, Sanchez C, Bressieux-Degueldre S, Perez MH, Wutz D, Blanchard-Rohner G, Grazioli S, Schobi N, Truck J, Welzel T, Atkinson A, Schlapbach LJ, Bielicki J; Swissped RECOVERY Trial Group. Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial. EClinicalMedicine. 2023 Dec 6;67:102358. doi: 10.1016/j.eclinm.2023.102358. eCollection 2024 Jan.

  PMID: 38107550 DERIVED

• Welzel T, Schobi N, Andre MC, Bailey DGN, Blanchard-Rohner G, Buettcher M, Grazioli S, Koehler H, Perez MH, Truck J, Vanoni F, Zimmermann P, Atkinson A, Sanchez C, Whittaker E, Faust SN, Bielicki JA, Schlapbach LJ; Swissped Recovery Trial. 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.

  PMID: 35669398 DERIVED

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

pediatric multisystem inflammatory disease, COVID-19 related; COVID-19

Interventions

Methylprednisolone Hemisuccinate; gamma-Globulins; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies

Study Officials

• Julia Bielicki, Dr. med.

  Paediatric Infectious Diseases and Vaccinology, Universität-Kinderspital beider Basel (UKBB)

  PRINCIPAL INVESTIGATOR

• Luregn Schlapbach, Dr. med.

  Pediatric and Neonatal Intensive Care Unit, University Children's Hospital Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Overarching trial design with treatment arms that are both available at the hospital and not believed by the enrolling doctor to be contraindicated (e.g. by particular co-morbid conditions or concomitant medications). Treatment arms to be added or removed according to the emerging evidence. Main randomisation part A: Methylprednisolone 2 mg/kg for three days intravenous or orally vs corticosteroids methylprednisolone 10mg/kg intravenous for three days vs intravenous immunoglobulin.

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 1, 2021
• Study Start: May 23, 2021
• Primary Completion: November 20, 2022
• Study Completion: November 20, 2022
• Last Updated: February 13, 2025

Record last verified: 2023-02

Locations

CH (10)