Clinical trial NCT04826588: Randomised Evaluation of COVID-19 Therapy (RECOVERY) in Children With PIMS-TS in Switzerland (SWISSPED-RECOVERY)
Official title: Randomised Evaluation of COVID-19 Therapy (RECOVERY) in Children With PIMS-TS in Switzerland (SWISSPED-RECOVERY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: University Children's Hospital Basel
Sponsor class: OTHER
Collaborators: name: SwissPedNet
First posted: 2021-04-01
Enrollment: 76
Sex: ALL
Minimum age (years): 44
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hospital length of stay
timeFrame: Within 28 days after randomisation
Secondary outcomes:
measure: All-cause mortality among patients
timeFrame: Within 28 days and up to 6 months after randomisation
measure: Composite endpoint of death or need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
timeFrame: Within 28 days and up to 6 months after randomisation
Other outcomes:
measure: Need for (and duration of) ventilation
timeFrame: Within 28 days and up to 6 months after randomisation
measure: Need for renal replacement therapy
timeFrame: Within 28 days and up to 6 months after randomisation
measure: Number of patients who had thrombotic events
timeFrame: Within 28 days and up to 6 months after randomisation
measure: Cardiac outcome (long-term impact) of PIMS-TS after discharge
timeFrame: Post-discharge extended follow-up visits up to 6 months after randomisation
measure: Neurological outcome (long-term impact) of PIMS-TS after discharge
timeFrame: Post-discharge extended follow-up visits up to 6 months after randomisation
measure: Health care costs
timeFrame: Within 28 days after randomisation
measure: Quality of life post-infection assessed by Strengths and Difficulties Questionnaire (SDQ)
timeFrame: Post-discharge extended follow-up visits up to 6 months after randomisation
Locations:
city: Aarau
country: Switzerland
facility: Cantonal Hospital Aarau, Department of Paediatrics
city: Basel
country: Switzerland
facility: University of Basel Children's Hospital
city: Bellinzona
country: Switzerland
facility: Ente Ospedaliero Cantonale Ticino (EOC) Pediatrica
city: Bern
country: Switzerland
facility: Department of Pediatrics, University of Bern
city: Geneva
country: Switzerland
facility: Department of Child, Woman and, Adolescent Medecine, Geneva University Hospitals and Faculty of Medicine
city: Lausanne
country: Switzerland
facility: Department of Pediatrics,University Hospital of Lausanne (CHUV)
city: Luzern 16
country: Switzerland
facility: Department of Pediatrics, Cantonal Hospital Luzern
city: St. Gallen
country: Switzerland
facility: Children's Hospital of Eastern Switzerland
city: Villars-sur-Glâne
country: Switzerland
facility: Department of Pediatrics, Cantonal Hospital Fribourg
city: Zuerich
country: Switzerland
facility: University Children's Hospital Zuerich
Study officials:
affiliation: Paediatric Infectious Diseases and Vaccinology, Universität-Kinderspital beider Basel (UKBB)
name: Julia Bielicki, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pediatric and Neonatal Intensive Care Unit, University Children's Hospital Zurich
name: Luregn Schlapbach, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.