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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

Eleftheriou, Despina ; Moraes, Yolanda Collaco ; Purvis, Cara ; Pursell, Molly ; Morillas, Marta Merida ; Kahn, Robin LU ; Mossberg, Maria LU ; Kucera, Filip ; Tulloh, Robert and Standing, Joseph F. , et al. (2023) In Trials 24(1).
Abstract

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.... (More)

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: 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: 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: ISRCTN71987471- March 31, 2020; Eudract 2019–004433-17.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Coronary artery aneurysms, Corticosteroids, Kawasaki disease
in
Trials
volume
24
issue
1
article number
60
publisher
BioMed Central (BMC)
external identifiers
  • pmid:36703139
  • scopus:85146946910
ISSN
1745-6215
DOI
10.1186/s13063-022-07051-9
language
English
LU publication?
yes
id
94afc7da-fecc-4a6e-b622-bb62eaf5b0c2
date added to LUP
2023-02-09 15:12:32
date last changed
2024-07-09 14:43:27
@article{94afc7da-fecc-4a6e-b622-bb62eaf5b0c2,
  abstract     = {{<p>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: 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: 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: ISRCTN71987471- March 31, 2020; Eudract 2019–004433-17.</p>}},
  author       = {{Eleftheriou, Despina and Moraes, Yolanda Collaco and Purvis, Cara and Pursell, Molly and Morillas, Marta Merida and Kahn, Robin and Mossberg, Maria and Kucera, Filip and Tulloh, Robert and Standing, Joseph F. and Swallow, Veronica and McCormack, Rachael and Herberg, Jethro and Levin, Michael and Wan, Mandy and Klein, Nigel and Connon, Roisin and Walker, Ann Sarah and Brogan, Paul}},
  issn         = {{1745-6215}},
  keywords     = {{Coronary artery aneurysms; Corticosteroids; Kawasaki disease}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Trials}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1186/s13063-022-07051-9}},
  doi          = {{10.1186/s13063-022-07051-9}},
  volume       = {{24}},
  year         = {{2023}},
}