학술논문
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.
Document Type
Academic Journal
Author
Andre MC; Division of Respiratory and Critical Care Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland.; Department of Pediatric Haematology and Oncology, University Children's Hospital, Eberhard Karls University, Tuebingen, Germany.; Sanchez C; Paediatric Research Centre, University Children's Hospital Basel, University of Basel, Basel, Switzerland.; Bressieux-Degueldre S; Paediatric Cardiology Unit, Department of Women-Mother-Child, University Hospital of Lausanne and Lausanne University, Lausanne, Switzerland.; Perez MH; Paediatric Intensive and Intermediate Care Units, Department of Women-Mother-Child, University Hospital of Lausanne and Lausanne University, Lausanne, Switzerland.; Wütz D; Division of Pediatric Cardiology, Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland.; Blanchard-Rohner G; Pediatric Immunology and Vaccinology Unit, Division of General Pediatrics, Department of Child, Woman and Adolescent Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.; Grazioli S; Division of Neonatal and Pediatric Intensive Care, Department of Child, Woman and Adolescent Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.; Schöbi N; Division of Pediatric Infectious Diseases, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Trück J; Divisions of Allergy and Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich (UZH), Zurich, Switzerland.; Welzel T; Paediatric Research Centre, University Children's Hospital Basel, University of Basel, Basel, Switzerland.; Pediatric Rheumatology, University Children's Hospital Basel, University of Basel, Basel, Switzerland.; Atkinson A; Paediatric Research Centre, University Children's Hospital Basel, University of Basel, Basel, Switzerland.; Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.; Schlapbach LJ; Department of Intensive Care and Neonatology, and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.; Paediatric Intensive Care Unit, Child Health Research Centre, Queensland Children's Hospital, The University of Queensland, Brisbane, Australia.; Bielicki J; Paediatric Research Centre, University Children's Hospital Basel, University of Basel, Basel, Switzerland.; Centre for Neonatal and Paediatric Infection, St George's University, London, United Kingdom.
Source
Publisher: The Lancet Country of Publication: England NLM ID: 101733727 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-5370 (Electronic) Linking ISSN: 25895370 NLM ISO Abbreviation: EClinicalMedicine Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population.
Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588).
Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39).
Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes.
Funding: NOMIS, Vontobel, and Gaydoul Foundation.
Competing Interests: LJS was supported by grants from the NOMIS Foundation, the Vontobel Foundation, and the Gaydoul Foundation for this study. Swiss PedNet (https://www.swisspednet.ch/) provided infrastructure support for study coordination and monitoring. JB received grant support paid to the institution from the European and Developing Countries Clinical Trials Partnership (PediCaP, RIA2017MC-2023), Horizon 2020 (NeoIPC, grant 965328), the Swiss National Science Foundation (KIDS-STEP, grant 173532), National Institute for Health Research (CAP-IT, project 13/88/11), Innosuisse (SPEARHEAD flagship grant), the Swiss Personalised Health Network (Secretariat for Education Research and Innovation) (SwissPedHealth, award NDS-2021-911), in the past 36 months; consulting fees paid to the institution from Shionogi, Sandoz, Basilea, and GSK; payments to the institution for presentations, lectures, speakers bureaus, manuscript writing or educational events in the past 36 months from Pfizer, Sandoz, and Bayer; participated at independent data monitoring committee boards of Avenir trial (member, expenses), Lakana trial (member, unfunded), CURLY trial (Chair, unfunded) in the past 36 months; is the vice president of the SwissPedNet (unpaid) and leadership of Severe Bacterial Infection and Antimicrobial Resistance working group of the Penta Foundation (unpaid). TW gave presentations for Novartis (payment to the institution) in the past 36 months. All other authors declare no competing interests.
(© 2023 The Author(s).)
Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588).
Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39).
Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes.
Funding: NOMIS, Vontobel, and Gaydoul Foundation.
Competing Interests: LJS was supported by grants from the NOMIS Foundation, the Vontobel Foundation, and the Gaydoul Foundation for this study. Swiss PedNet (https://www.swisspednet.ch/) provided infrastructure support for study coordination and monitoring. JB received grant support paid to the institution from the European and Developing Countries Clinical Trials Partnership (PediCaP, RIA2017MC-2023), Horizon 2020 (NeoIPC, grant 965328), the Swiss National Science Foundation (KIDS-STEP, grant 173532), National Institute for Health Research (CAP-IT, project 13/88/11), Innosuisse (SPEARHEAD flagship grant), the Swiss Personalised Health Network (Secretariat for Education Research and Innovation) (SwissPedHealth, award NDS-2021-911), in the past 36 months; consulting fees paid to the institution from Shionogi, Sandoz, Basilea, and GSK; payments to the institution for presentations, lectures, speakers bureaus, manuscript writing or educational events in the past 36 months from Pfizer, Sandoz, and Bayer; participated at independent data monitoring committee boards of Avenir trial (member, expenses), Lakana trial (member, unfunded), CURLY trial (Chair, unfunded) in the past 36 months; is the vice president of the SwissPedNet (unpaid) and leadership of Severe Bacterial Infection and Antimicrobial Resistance working group of the Penta Foundation (unpaid). TW gave presentations for Novartis (payment to the institution) in the past 36 months. All other authors declare no competing interests.
(© 2023 The Author(s).)