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

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.

Study Overview

• Status: Completed
• Conditions: Paediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS)
• Intervention / Treatment: Drug: Methylprednisolone sodium succinate 10 mg/kg intravenously; Biological: Human normal immunoglobulin (IVIg)

Detailed Description

In May 2020 a new COVID-associated inflammatory syndrome in children was identified, Paediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). A rapid international consensus process identified the need to evaluate corticosteroids and intravenous immunoglobulin (IVIg) as initial therapies in PIMS-TS, and confirmed tocilizumab and anakinra as biological anti-inflammatory agents to be evaluated as a second line therapy.

This Swissped-Recovery trial is a sister trial to the RECOVERY international trial with the implementation of the study at Swiss study sites.

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.

Additional substudies can be added to provide more detailed information on side effects or sub-categorisation of patient types.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Cantonal Hospital Aarau, Department of Paediatrics
  • Basel, Switzerland, 4056
    • University of Basel Children's Hospital
  • Bellinzona, Switzerland, 6500
    • Ente Ospedaliero Cantonale Ticino (EOC) Pediatrica
  • Bern, Switzerland, 3010
    • Department of Pediatrics, University of Bern
  • Geneva, Switzerland
    • Department of Child, Woman and, Adolescent Medecine, Geneva University Hospitals and Faculty of Medicine
  • Lausanne, Switzerland
    • Department of Pediatrics,University Hospital of Lausanne (CHUV)
  • Luzern 16, Switzerland, 6000
    • Department of Pediatrics, Cantonal Hospital Luzern
  • St. Gallen, Switzerland, 9006
    • Children's Hospital of Eastern Switzerland
  • Villars-sur-Glâne, Switzerland, 1752
    • Department of Pediatrics, Cantonal Hospital Fribourg
  • Zuerich, Switzerland, 8032
    • University Children's Hospital Zuerich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methylprednisolone sodium succinate 10 mg/kg; 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; Methylprednisolone sodium succinate 10 mg/kg intravenously once daily for 3 days (max 1 g per dose)
Active Comparator: Human normal immunoglobulin (IVIg); 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); Human normal immunoglobulin (IVIg) 2g/kg intravenously as a single dose in line with guidance for dosing and administration in Kawasaki disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay	effect of study treatment on hospital length of stay	Within 28 days after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality among patients	For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.	Within 28 days and up to 6 months after randomisation
Composite endpoint of death or need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO)	Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO.	Within 28 days and up to 6 months after randomisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for (and duration of) ventilation	To assess the effects of study treatment on number of patients who needed any ventilation and (for invasive mechanical ventilation) the number of days it was required	Within 28 days and up to 6 months after randomisation
Need for renal replacement therapy	To assess the effects of study treatment on number of patients who needed renal replacement therapy	Within 28 days and up to 6 months after randomisation
Number of patients who had thrombotic events	To assess the effects of study treatment on number of patients who had thrombotic events	Within 28 days and up to 6 months after randomisation
Cardiac outcome (long-term impact) of PIMS-TS after discharge	Cardiac function and presence of coronary artery aneurysms will be assessed by echocardiography.	Post-discharge extended follow-up visits up to 6 months after randomisation
Neurological outcome (long-term impact) of PIMS-TS after discharge	assessment of post-traumatic stress disorder	Post-discharge extended follow-up visits up to 6 months after randomisation
Health care costs	Direct hospitalization-related costs will be captured for health economic analyses. For each PIMS-TS related hospitalization episode recruited in the study, the total Diagnosis-Related Group (DRG) costs claimed by the respective study site will be extracted from the institutional finance records, and analysed in batch upon completion of recruitment	Within 28 days after randomisation
Quality of life post-infection assessed by Strengths and Difficulties Questionnaire (SDQ)	The strengths and difficulties questionnaire (SDQ) is a short behavioural screening questionnaire for children aged 3 to 16. The 25 personality attributes in the SDQ are made up of 5 scales of 5 items each. The scales are: Emotional symptoms, Conduct problems, Hyperactivity/inattention, Peer relationship problems, Prosocial behaviour. Each subscale includes five items, rating each item as either: Never = 0, Somewhat True = 1 or Certainly True = 2. SDQ total scores of 17 and above are considered to be abnormal.	Post-discharge extended follow-up visits up to 6 months after randomisation

Collaborators and Investigators

• Sponsor: University Children's Hospital Basel

Publications and helpful links

General Publications

• 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.
• 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.
• 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 Feb 3:S2352-4642(23)00020-2. doi: 10.1016/S2352-4642(23)00020-2. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2021
• Primary Completion (Actual): November 20, 2022
• Study Completion (Actual): November 20, 2022

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: tocilizumab; anakinra; coronavirus-disease (COVID-19); SARS coronavirus 2 (SARS-CoV-2); Human normal immunoglobulin (IVIg); Methylprednisolone sodium succinate
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Immunoglobulins
• Other Study ID Numbers: 2021-00362; ks21Bielicki2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No