Schöbi, N;
Sanchez, C;
Welzel, T;
Bamford, A;
Webb, K;
Rojo, P;
Tremoulet, A;
Atkinson, A;
Schlapbach, LJ;
Bielicki, JA;
et al.
Schöbi, N; Sanchez, C; Welzel, T; Bamford, A; Webb, K; Rojo, P; Tremoulet, A; Atkinson, A; Schlapbach, LJ; Bielicki, JA; Swissped-RECOVERY trial group
(2024)
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, 14 (4).
e078137.
ISSN 2044-6055
https://doi.org/10.1136/bmjopen-2023-078137
SGUL Authors: Bielicki, Julia Anna
Abstract
OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588.
Item Type: |
Article
|
Additional Information: |
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
Keywords: |
SARS-CoV-2 infection, paediatric infectious disease & immunisation, paediatric intensive & critical care, post-infectious disorders, randomized controlled trial, Humans, Methylprednisolone, Systemic Inflammatory Response Syndrome, Child, Switzerland, COVID-19, Immunoglobulins, Intravenous, Adolescent, SARS-CoV-2, Hospitals, Pediatric, COVID-19 Drug Treatment, Female, Male, Anti-Inflammatory Agents, Child, Preschool, Treatment Outcome, Swissped-RECOVERY trial group, Humans, Methylprednisolone, Immunoglobulins, Intravenous, Anti-Inflammatory Agents, Treatment Outcome, Adolescent, Child, Child, Preschool, Hospitals, Pediatric, Switzerland, Female, Male, Systemic Inflammatory Response Syndrome, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, 1103 Clinical Sciences, 1117 Public Health and Health Services, 1199 Other Medical and Health Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
BMJ Open |
ISSN: |
2044-6055 |
Language: |
eng |
Dates: |
Date | Event |
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25 April 2024 | Published | 25 March 2024 | Accepted |
|
Publisher License: |
Creative Commons: Attribution-Noncommercial 4.0 |
Projects: |
|
PubMed ID: |
38670610 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116472 |
Publisher's version: |
https://doi.org/10.1136/bmjopen-2023-078137 |
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