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

Primary Purpose

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

Status

Completed

Phase

Phase 3

Locations

Switzerland

Study Type

Interventional

Intervention

Methylprednisolone sodium succinate 10 mg/kg intravenously

Human normal immunoglobulin (IVIg)

About this trial

This is an interventional treatment trial for Paediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS) focused on measuring coronavirus-disease (COVID-19), SARS coronavirus 2 (SARS-CoV-2), tocilizumab, anakinra, Human normal immunoglobulin (IVIg), Methylprednisolone sodium succinate

Eligibility Criteria

44 Weeks - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Cantonal Hospital Aarau, Department of Paediatrics
University of Basel Children's Hospital
Ente Ospedaliero Cantonale Ticino (EOC) Pediatrica
Department of Pediatrics, University of Bern
Department of Child, Woman and, Adolescent Medecine, Geneva University Hospitals and Faculty of Medicine
Department of Pediatrics,University Hospital of Lausanne (CHUV)
Department of Pediatrics, Cantonal Hospital Luzern
Children's Hospital of Eastern Switzerland
Department of Pediatrics, Cantonal Hospital Fribourg
University Children's Hospital Zuerich

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Methylprednisolone sodium succinate 10 mg/kg

Human normal immunoglobulin (IVIg)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Hospital length of stay

effect of study treatment on hospital length of stay

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT04826588

First Posted

March 31, 2021

Last Updated

February 20, 2023

Sponsor

University Children's Hospital Basel

1. Study Identification

Unique Protocol Identification Number

NCT04826588

Brief Title

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

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

May 23, 2021 (Actual)

Primary Completion Date

November 20, 2022 (Actual)

Study Completion Date

November 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Children's Hospital Basel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

76 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Methylprednisolone sodium succinate 10 mg/kg

Arm Type

Active Comparator

Arm Description

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

Arm Title

Human normal immunoglobulin (IVIg)

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Methylprednisolone sodium succinate 10 mg/kg intravenously

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Human normal immunoglobulin (IVIg)

Intervention Description

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

Primary Outcome Measure Information:

Title

Hospital length of stay

Description

effect of study treatment on hospital length of stay

Time Frame

Within 28 days after randomisation

Secondary Outcome Measure Information:

Title

All-cause mortality among patients

Description

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.

Time Frame

Within 28 days and up to 6 months after randomisation

Title

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

Description

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.

Time Frame

Within 28 days and up to 6 months after randomisation

Other Pre-specified Outcome Measures:

Title

Need for (and duration of) ventilation

Description

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

Time Frame

Within 28 days and up to 6 months after randomisation

Title

Need for renal replacement therapy

Description

To assess the effects of study treatment on number of patients who needed renal replacement therapy

Time Frame

Within 28 days and up to 6 months after randomisation

Title

Number of patients who had thrombotic events

Description

To assess the effects of study treatment on number of patients who had thrombotic events

Time Frame

Within 28 days and up to 6 months after randomisation

Title

Cardiac outcome (long-term impact) of PIMS-TS after discharge

Description

Cardiac function and presence of coronary artery aneurysms will be assessed by echocardiography.

Time Frame

Post-discharge extended follow-up visits up to 6 months after randomisation

Title

Neurological outcome (long-term impact) of PIMS-TS after discharge

Description

assessment of post-traumatic stress disorder

Time Frame

Post-discharge extended follow-up visits up to 6 months after randomisation

Title

Health care costs

Description

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

Time Frame

Within 28 days after randomisation

Title

Quality of life post-infection assessed by Strengths and Difficulties Questionnaire (SDQ)

Description

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.

Time Frame

Post-discharge extended follow-up visits up to 6 months after randomisation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

44 Weeks

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Julia Bielicki, Dr. med.

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Luregn Schlapbach, Dr. med.

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cantonal Hospital Aarau, Department of Paediatrics

City

Aarau

ZIP/Postal Code

5001

Country

Switzerland

Facility Name

University of Basel Children's Hospital

City

Basel

ZIP/Postal Code

4056

Country

Switzerland

Facility Name

Ente Ospedaliero Cantonale Ticino (EOC) Pediatrica

City

Bellinzona

ZIP/Postal Code

6500

Country

Switzerland

Facility Name

Department of Pediatrics, University of Bern

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Facility Name

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

City

Geneva

Country

Switzerland

Facility Name

Department of Pediatrics,University Hospital of Lausanne (CHUV)

City

Lausanne

Country

Switzerland

Facility Name

Department of Pediatrics, Cantonal Hospital Luzern

City

Luzern 16

ZIP/Postal Code

6000

Country

Switzerland

Facility Name

Children's Hospital of Eastern Switzerland

City

St. Gallen

ZIP/Postal Code

9006

Country

Switzerland

Facility Name

Department of Pediatrics, Cantonal Hospital Fribourg

City

Villars-sur-Glâne

ZIP/Postal Code

1752

Country

Switzerland

Facility Name

University Children's Hospital Zuerich

City

Zuerich

ZIP/Postal Code

8032

Country

Switzerland

12. IPD Sharing Statement

Citations:

PubMed Identifier

36746174

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. Erratum In: Lancet Child Adolesc Health. 2023 Apr;7(4):e10.

Results Reference

result

PubMed Identifier

35669398

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.

Results Reference

derived

PubMed Identifier

34473343

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.

Results Reference

derived

Learn more about this trial

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

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