About KD-CAAP

Kawasaki Disease Coronary Artery Aneurysm Prevention trial, or KD-CAAP is a phase III 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).

A number of recent studies conducted in different European countries (UK, Sweden, and Germany), Russia, and the United States have recently demonstrated alarmingly high rates of coronary complications despite IVIG. Coronary artery aneurysm (CAA) rates ranged from 16% in the Swedish study (45% in infants under 12 months), to as high as 42% in younger children in the German survey. In the UK, a recent survey (2013-2015) suggested that 19% of children with KD still developed CAA despite IVIG; and, even more worryingly in that survey, 39% of patients under the age of 1 year developed CAA despite IVIG [7]. These high complication rates now emphasise the need for an urgent reappraisal of IVIG and aspirin as the primary therapeutic agents for KD.

We have recently published evidence-based, consensus European guidelines for the diagnosis and treatment of KD and in doing so clearly observed:

    1. Higher CAA rates than previously considered to be associated with IVIG-treated KD;
    2. Important evidence gaps regarding lack of an appropriate clinical tool to stratify patients at highest risk of CAA outside of Japan, and hence who to target for more aggressive treatment; and
    3. Significant equipoise among the paediatric community across Europe regarding the use of adjunctive treatments for unselected KD cases.

These observations have been important drivers for a trial to improve KD outcomes across Europe. The KD-CAAP trial is a multi-centre randomised, controlled, open-label, blinded endpoint assessed, trial to explore the efficacy and safety of adjunctive corticosteroid therapy combined with IVIG/aspirin, versus IVIG/aspirin alone in unselected KD cases across Europe.

Corticosteroids are an effective treatment for virtually all forms of vasculitis, but they have not been adopted as first-line treatment of unselected KD cases, for which there remains significant equipoise. Increasingly compelling evidence summarised above from randomised controlled trials and meta-analyses supports corticosteroid use as primary adjunctive treatment for patients with severe KD, particularly for Japanese patients with a Kobayashi score ≥5, and for whom CAA risk is 20-30% despite IVIG. This does not, however, resolve the ongoing debate about which KD patients should be considered as “severe” outside of Japan, since the Kobayashi score and other clinical severity-scoring systems have poor predictive value in non-Japanese patients. Given however, the aforementioned high CAA complication rates seen across Europe (16-45%), all KD patients are arguably at high-risk of CAA despite IVIG, and could therefore potentially benefit from adjunctive corticosteroids as primary treatment for KD. Therefore there remains significant equipoise regarding the use of corticosteroids as primary treatment combined with IVIG for all patients, i.e. not just the most severe cases.

Overall Trial Management: KD-CAAP is managed by the Medical Research Council (MRC) Clinical Trials Unit (KD-CAAP Co-ordinating Centre).

Trial sponsor: KD-CAAP is sponsored by University College London (UCL). 

Funding: Innovative Medicines Initiative 2 Joint Undertaking (JU) that supports the conect4children (c4c) research consortium

 Aims and Objectives

The aim of the KD-CAAP trial is to determine whether adding immediate corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe compared with IVIG and aspirin alone.

 

KD-CAAP
Coordinating Centre

MRC Clinical Trials Unit at UCL
90 High Holborn
2nd Floor 
London
WC1V 6LJ

Email: mrcctu.kdcaap@ucl.ac.uk