Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD CAA prevention (KD-CAAP) trial protocol.
Child
Humans
Infant
Adrenal Cortex Hormones
/ adverse effects
Aneurysm
/ complications
Aspirin
/ adverse effects
Coronary Vessels
Immunoglobulins, Intravenous
/ adverse effects
Mucocutaneous Lymph Node Syndrome
/ complications
Multicenter Studies as Topic
Quality of Life
Randomized Controlled Trials as Topic
Child, Preschool
Adolescent
Coronary artery aneurysms
Corticosteroids
Kawasaki disease
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
26 Jan 2023
26 Jan 2023
Historique:
received:
28
10
2022
accepted:
23
12
2022
entrez:
26
1
2023
pubmed:
27
1
2023
medline:
31
1
2023
Statut:
epublish
Résumé
Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe. KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes. Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children. ISRCTN71987471- March 31, 2020; Eudract 2019-004433-17.
Sections du résumé
BACKGROUND
BACKGROUND
Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe.
METHODS
METHODS
KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes.
DISCUSSION
CONCLUSIONS
Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children.
TRIAL REGISTRATION
BACKGROUND
ISRCTN71987471- March 31, 2020; Eudract 2019-004433-17.
Identifiants
pubmed: 36703139
doi: 10.1186/s13063-022-07051-9
pii: 10.1186/s13063-022-07051-9
pmc: PMC9879235
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Aspirin
R16CO5Y76E
Immunoglobulins, Intravenous
0
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
60Subventions
Organisme : Medical Research Council
ID : MR/M008665/1
Pays : United Kingdom
Organisme : Innovative Medicines Initiative
ID : 777389
Informations de copyright
© 2023. The Author(s).
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