Trial Summary

This study will work out the best way to treat children and adolescents aged between 30 days and 15 years who have Kawasaki disease. Kawasaki disease is a disease where arteries, particularly the coronary arteries in the heart, become inflamed, sometimes causing irreversible heart damage, heart attacks or even death. Kawasaki disease is currently the most common cause of acquired heart disease in childhood, and an important preventable cause of heart disease in the young. These heart complications may occur within a few weeks of getting the disease, or more typically, some years after recovery due to narrowing of the coronary arteries causing lack of blood supply to the heart. To prevent this heart damage, the fact that a child or young person has Kawasaki disease has to be recognised by clinicians early, and promptly treated with anti-inflammatory medicines.

The problem is that Kawasaki disease presents with a range of symptoms that are common in normal childhood infections, including a high fever for five days or more, rash, bloodshot eyes, “strawberry” red tongue, cracked, dry lips, swollen lymph glands in the neck, and redness and swelling of the palms and soles. No one knows what causes Kawasaki disease, and this is an area of ongoing and intense research around the world. Experts suggest that wind borne toxins derived from agriculture might be important triggers, combined with genetic susceptibility, although this is by no means firmly established. As such, there is no laboratory diagnostic test available for Kawasaki disease, and diagnosis therefore depends on early recognition of the clinical features.

Intravenous immunoglobulin (IVIG) is a blood product derived from many different pooled healthy blood donors, containing antibodies naturally produced by the immune system. IVIG is the standard treatment given in Kawasaki disease to “dampen down” inflammatory processes which occur in the first few days of the illness. Many children and adolescents still develop significant heart damage despite IVIG. In the UK, heart damage has been found in 19% of cases despite IVIG; in other countries it is as high as 42%. Corticosteroids (‘steroids’) have been used for decades to treat similar inflammatory conditions, but are not yet widely used as an initial treatment for Kawasaki disease. In this study, we will work out if giving corticosteroids upfront (in addition to IVIG) to children and adolescents with Kawasaki disease across Europe reduces the high rate of heart complications we are currently observing.

 All children and adolescents in the study will get the current recommended standard treatment of IVIG and aspirin. They will then be split into two groups, by chance (called “randomisation”). One group will not receive any extra treatment other than the standard IVIG and aspirin. The second group will receive additional treatment with prednisolone (corticosteroids) by mouth (or intravenously, into a vein, if needed) immediately. They will take steroids for around 2-3 weeks, depending on how quickly they get better. Everyone will have frequent assessments of their inflammatory status (temperature and inflammatory blood test markers) to work out whether they still need additional IVIG treatment 2 days after they start treatment. Five days later, they will all be re-evaluated again to work out whether they still need extra treatment if the inflammation has not settled completely. Whichever group they started in, children and adolescents will get any extra treatment they then need.

 We will follow children and adolescents for 12 weeks through face-to-face visits to find out whether they have had any problems – they will mostly stay in hospital for the first 5-7 days, and there are just three visits after this first week. This duration of follow-up is standard for routine clinical care of Kawasaki disease. We will particularly focus on

  • looking for any damage to their coronary arteries (or other heart damage) using heart ultrasound (echocardiography) scans;
  • whether they experienced any side effects from the medicines they received;
  • whether they needed to receive any additional treatments; how long they had to stay in hospital;
  • whether they have to be admitted to hospital again;
  • how rapidly their blood tests normalised;
  • how much all their care costs; and
  • If our treatments overall improve their quality of life

In summary, in this study we will answer all of the following questions to work out the best way to treat children and adolescents aged 30 days to 15 years who have Kawasaki disease:

  1. Does the combination of corticosteroid and IVIG/aspirin reduce the rate of heart complications in children/adolescents with Kawasaki disease across Europe? (main question)
  2. Does the combination of corticosteroid and IVIG/aspirin reduce the length of stay in hospital for children/adolescents with Kawasaki disease, and do their blood test results improve faster?
  3. What side effects do children/adolescents get with corticosteroids or other therapies to treat Kawasaki disease?
  4. Is the combination of corticosteroid therapy and IVIG/aspirin a cost effective treatment for the management of Kawasaki disease?

Coordinating Centre

MRC Clinical Trials Unit at UCL
90 High Holborn
2nd Floor