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, 2024 Apr 25.
Article
in En
| MEDLINE
| ID: mdl-38670610
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Methylprednisolone
/
Immunoglobulins, Intravenous
/
Systemic Inflammatory Response Syndrome
/
SARS-CoV-2
/
COVID-19
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
BMJ Open
Year:
2024
Type:
Article
Affiliation country:
Switzerland