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| Name | Class |
|---|---|
| SwissPedNet | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hospital length of stay | effect of study treatment on hospital length of stay | Within 28 days after randomisation |
| 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) |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cantonal Hospital Aarau, Department of Paediatrics | Aarau | 5001 | Switzerland | |||
| University of Basel Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36746174 | Result | 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. | |
| 38670610 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 18, 2022 |
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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.
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| 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 |
|
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 |
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 |
| Basel |
| 4056 |
| Switzerland |
| Ente Ospedaliero Cantonale Ticino (EOC) Pediatrica | Bellinzona | 6500 | Switzerland |
| Department of Pediatrics, University of Bern | Bern | 3010 | Switzerland |
| Department of Child, Woman and, Adolescent Medecine, Geneva University Hospitals and Faculty of Medicine | Geneva | Switzerland |
| Department of Pediatrics,University Hospital of Lausanne (CHUV) | Lausanne | Switzerland |
| Department of Pediatrics, Cantonal Hospital Luzern | Lucerne | 6000 | Switzerland |
| Children's Hospital of Eastern Switzerland | Sankt Gallen | 9006 | Switzerland |
| Department of Pediatrics, Cantonal Hospital Fribourg | Villars-sur-Glâne | 1752 | Switzerland |
| University Children's Hospital Zuerich | Zurich | 8032 | Switzerland |
| Derived |
| 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. |
| 38107550 | 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. |
| 35669398 | 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. |
| 34473343 | 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. |
| Jan 17, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| C000705967 | pediatric multisystem inflammatory disease, COVID-19 related |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D008776 | Methylprednisolone Hemisuccinate |
| D005719 | gamma-Globulins |
| D016756 | Immunoglobulins, Intravenous |
| ID | Term |
|---|---|
| D008775 | Methylprednisolone |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
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