INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial

Introduction Asthma is a leading cause of morbidity and healthcare use among children. Risk factors of childhood asthma include atopic predisposition and severe wheezing episodes caused by rhinovirus infection in early life. In children with first-time rhinovirus-induced wheezing, we aim to study th...

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Main Authors: Maria Vollsæter, Knut Øymar, Svein Arne Nordbø, Tytti Vuorinen, Kari Risnes, Claus Klingenberg, Tuomas Jartti, Henrik Døllner, Anna Partty, Håvard Ove Skjerven, Turid Follestad, Trude Elvebakk, Heidi Jartti, Silje Nerheim, Nina Moe, Johanna Koski, Anita Hofstad, Carina Bjørkvoll Leknessund, Cilla Söderhäll, Erle Sissener, Christopher Stephen Inchley, Jon R Konradsen
Format: Article
Language:English
Published: BMJ Publishing Group 2025-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/7/e103530.full
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author Maria Vollsæter
Knut Øymar
Svein Arne Nordbø
Tytti Vuorinen
Kari Risnes
Claus Klingenberg
Tuomas Jartti
Henrik Døllner
Anna Partty
Håvard Ove Skjerven
Turid Follestad
Trude Elvebakk
Heidi Jartti
Silje Nerheim
Nina Moe
Johanna Koski
Anita Hofstad
Carina Bjørkvoll Leknessund
Cilla Söderhäll
Erle Sissener
Christopher Stephen Inchley
Jon R Konradsen
author_facet Maria Vollsæter
Knut Øymar
Svein Arne Nordbø
Tytti Vuorinen
Kari Risnes
Claus Klingenberg
Tuomas Jartti
Henrik Døllner
Anna Partty
Håvard Ove Skjerven
Turid Follestad
Trude Elvebakk
Heidi Jartti
Silje Nerheim
Nina Moe
Johanna Koski
Anita Hofstad
Carina Bjørkvoll Leknessund
Cilla Söderhäll
Erle Sissener
Christopher Stephen Inchley
Jon R Konradsen
author_sort Maria Vollsæter
collection DOAJ
description Introduction Asthma is a leading cause of morbidity and healthcare use among children. Risk factors of childhood asthma include atopic predisposition and severe wheezing episodes caused by rhinovirus infection in early life. In children with first-time rhinovirus-induced wheezing, we aim to study the response of a short corticosteroid treatment to prevent recurrent wheezing and asthma.Method and analysis This is a double-blind, randomised, placebo-controlled, phase IV, international multicentre trial involving eight sites in Norway, Sweden and Finland. Two hundred and eighty 3–23 months old steroid-naïve children are randomised 1:1 to receive oral dexamethasone (0.3 mg/kg/day) versus placebo in 3 days for their first wheezing episode and rhinovirus infection. Rhinovirus is diagnosed with multiplex PCR. The two co-primary outcomes are time to next physician-confirmed wheezing episode, and time to asthma, within 24 months from inclusion. Asthma is defined as fulfilment of the 2007 National Asthma Education and Prevention Program—criteria for initiating asthma controller medication in children aged 0–4 years. Primary interaction analyses are age, gender, atopic predisposition, risk genotypes and viral co-detection. The optimal cut-off on the rhinovirus genome load used to define a true rhinovirus infection will be assessed by exploring interactions between rhinovirus genomic loads and study drug on the co-primary outcomes. Secondary outcomes are number of wheezing episodes, duration and severity of each wheezing episode, bronchial hyperreactivity, quality of life and safety (height/weight development) at 24 months from inclusion.Ethics and dissemination Rhinovirus positive children with acute wheezing fulfilling inclusion and exclusion criteria are enrolled after informed consent from both caregivers. This trial has received ethical approval from all sites. Results will be submitted to Competent Authorities and disseminated via peer-reviewed publications and conferences within paediatrics and other relevant fields. If proven effective, findings may be implemented directly into paediatric clinical guidelines.Trial registration number NCT03889743.
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spelling doaj-art-4ecdb4455b76414cbda155483af3a8e62025-08-20T03:58:36ZengBMJ Publishing GroupBMJ Open2044-60552025-07-0115710.1136/bmjopen-2025-103530INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trialMaria Vollsæter0Knut Øymar1Svein Arne Nordbø2Tytti Vuorinen3Kari Risnes4Claus Klingenberg5Tuomas Jartti6Henrik Døllner7Anna Partty8Håvard Ove Skjerven9Turid Follestad10Trude Elvebakk11Heidi Jartti12Silje Nerheim13Nina Moe14Johanna Koski15Anita Hofstad16Carina Bjørkvoll Leknessund17Cilla Söderhäll18Erle Sissener19Christopher Stephen Inchley20Jon R Konradsen2112 Haukeland University Hospital, Bergen, Norway6 Department of Paediatrics, Stavanger University Hospital, Stavanger, Norway8 Instiute of clinical and molecular medicine, Norwegian University of Science and Technology Faculty of Medicine and Health Sciences, Trondheim, Norway4 Department of Clinical Microbiology, TYKS Turku University Hospital, Turku, Finland1 Children’s Clinic, St Olav’s Hospital HF, Trondheim, Norway13 Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway3 TYKS Turku University Hospital Department of Paediatrics and Adolescent Medicine, Turku, Finland1 Children’s Clinic, St Olav’s Hospital HF, Trondheim, Norway3 TYKS Turku University Hospital Department of Paediatrics and Adolescent Medicine, Turku, Finland14 Oslo University Hospital Division of Paediatric and Adolescent Medicine, Oslo, Norway10 Department of Public Health and Nursing, Norwegian University of Science and Technology Faculty of Medicine and Health Sciences, Trondheim, Norway1 Children’s Clinic, St Olav’s Hospital HF, Trondheim, Norway3 TYKS Turku University Hospital Department of Paediatrics and Adolescent Medicine, Turku, Finland6 Department of Paediatrics, Stavanger University Hospital, Stavanger, Norway1 Children’s Clinic, St Olav’s Hospital HF, Trondheim, Norway11 Karolinska University Hospital, Stockholm, Sweden12 Haukeland University Hospital, Bergen, Norway13 Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway11 Karolinska University Hospital, Stockholm, Sweden16 Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway16 Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway11 Karolinska University Hospital, Stockholm, SwedenIntroduction Asthma is a leading cause of morbidity and healthcare use among children. Risk factors of childhood asthma include atopic predisposition and severe wheezing episodes caused by rhinovirus infection in early life. In children with first-time rhinovirus-induced wheezing, we aim to study the response of a short corticosteroid treatment to prevent recurrent wheezing and asthma.Method and analysis This is a double-blind, randomised, placebo-controlled, phase IV, international multicentre trial involving eight sites in Norway, Sweden and Finland. Two hundred and eighty 3–23 months old steroid-naïve children are randomised 1:1 to receive oral dexamethasone (0.3 mg/kg/day) versus placebo in 3 days for their first wheezing episode and rhinovirus infection. Rhinovirus is diagnosed with multiplex PCR. The two co-primary outcomes are time to next physician-confirmed wheezing episode, and time to asthma, within 24 months from inclusion. Asthma is defined as fulfilment of the 2007 National Asthma Education and Prevention Program—criteria for initiating asthma controller medication in children aged 0–4 years. Primary interaction analyses are age, gender, atopic predisposition, risk genotypes and viral co-detection. The optimal cut-off on the rhinovirus genome load used to define a true rhinovirus infection will be assessed by exploring interactions between rhinovirus genomic loads and study drug on the co-primary outcomes. Secondary outcomes are number of wheezing episodes, duration and severity of each wheezing episode, bronchial hyperreactivity, quality of life and safety (height/weight development) at 24 months from inclusion.Ethics and dissemination Rhinovirus positive children with acute wheezing fulfilling inclusion and exclusion criteria are enrolled after informed consent from both caregivers. This trial has received ethical approval from all sites. Results will be submitted to Competent Authorities and disseminated via peer-reviewed publications and conferences within paediatrics and other relevant fields. If proven effective, findings may be implemented directly into paediatric clinical guidelines.Trial registration number NCT03889743.https://bmjopen.bmj.com/content/15/7/e103530.full
spellingShingle Maria Vollsæter
Knut Øymar
Svein Arne Nordbø
Tytti Vuorinen
Kari Risnes
Claus Klingenberg
Tuomas Jartti
Henrik Døllner
Anna Partty
Håvard Ove Skjerven
Turid Follestad
Trude Elvebakk
Heidi Jartti
Silje Nerheim
Nina Moe
Johanna Koski
Anita Hofstad
Carina Bjørkvoll Leknessund
Cilla Söderhäll
Erle Sissener
Christopher Stephen Inchley
Jon R Konradsen
INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial
BMJ Open
title INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial
title_full INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial
title_fullStr INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial
title_full_unstemmed INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial
title_short INnovative Steroid Treatment to reduce Asthma development in children after first-time Rhinovirus-induced wheezing (INSTAR): protocol for a randomised placebo-controlled trial
title_sort innovative steroid treatment to reduce asthma development in children after first time rhinovirus induced wheezing instar protocol for a randomised placebo controlled trial
url https://bmjopen.bmj.com/content/15/7/e103530.full
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