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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

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

Intervention / Treatment
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* Drug: Methylprednisolone sodium succinate 10 mg/kg intravenously
* Biological: Human normal immunoglobulin (IVIg)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 44 Weeks
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronavirus-disease (COVID-19), SARS coronavirus 2 (SARS-CoV-2), tocilizumab, anakinra, Human normal immunoglobulin (IVIg), Methylprednisolone sodium succinate