Kawasaki Disease Coronary Artery Aneurysm Prevention trial (KD-CAAP)

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).

In set-up

Aims of the study

KD-CAAP aims to find out whether or not giving an extra drug, called prednisolone (a steroid), for 2-3 weeks on top of the standard intravenous immunoglobulin (IVIG) and aspirin, will reduce coronary artery aneurysm rates in children and young people with Kawasaki disease compared to the standard treatment alone.

Inclusion criteria:

  • Aged between 30 days to 15 years, inclusive and below the county-age specific age of consent for the duration of the trial
  • Written informed consent from appropriate legal representative(s) and assent from patients who have not reached the age of consent and will not reach the age of consent for the duration of the trial in the participating country, but are judged to have the capacity for this (depending on both age and acuity of illness)

KD is defined in at least one of the three following ways:

1. As per American Heart Association (AHA) criteria: namely fever at least 5 days in addition to 4 of the following 5 clinical criteria:

  1. Bilateral non-purulent conjunctivitis
  2. Cervical lymphadenopathy
  3. Polymorphous skin rash
  4. Changes in lips or mucosa (strawberry tongue, red cracked lips, diffuse erythematous oropharynx)
  5. Extremity changes (erythema, oedema of palms and soles in initial phase, and at convalescent stage skin peeling

2. OR less than 5 days of fever but all 5 clinical criteria above

3. OR incomplete KD case, as per a modified AHA definition, namely:

  • Children/adolescents (>1-year-old) with a fever greater than or equal to 5 daysAND at least 2 other compatible clinical criteria as listed above; OR infants ≤1-year old with a fever greater than or equal to 7 days without other explanation;

AND for both age groups

  • C-reactive protein ≥30 mg/L or erythrocyte sedimentation rate (ESR) ≥40 mm/hr (or both)
  • EITHER the presence of any 3 or more of: anaemia for age; platelet count ≥450 x10⁹/L or <140 x10⁹/L; albumin <30g/L; elevated alanine aminotransferase (ALT); white cell count ≥15 x10⁹/L; urine ≥10 white blood cells per high power field
  • OR abnormal echocardiogram compatible with KD but without established CAA, with ≥3 of the following suggestive features: decreased left ventricular function, mitral regurgitation, pericardial effusion or dilated but non-aneurysmal coronary arteries

Exclusion criteria:

1. Disease-related exclusions:

  • This diagnosis is a second or further episode of KD
  • Already established CAA at screening
  • Severe Congestive Heart Failure or cardiogenic shock defined as the presence of hypotension and shock requiring the initiation of volume expanders
  • Known congenital coronary artery abnormality that would impair the assessment of the primary endpoint
  • Suspected macrophage activation syndrome

2. Exclusions related to medications:

  • Started IVIG more than 24 hours prior to randomisation
  • Known hypersensitivity to prednisolone or methylprednisolone
  • Current oral, intravenous or intramuscular corticosteroid treatment for more than 3 days in the previous 7 days prior to randomisation
  • History of previous severe reaction to any human immune globulin preparation

3. Exclusions related to general health or other issues:

  • Active varicella zoster virus infection; or known exposure to a case of varicella within the previous 21 days prior to randomisation if known to be non-immune
  • Co-enrolment in another study/trial of an investigative medicinal product

What participating in the study involves

Children and young people will get the same standard treatment (IVIG and aspiring) whether or not they join the study. Half of the people in the study will get an extra drug, prednisolone for 2-3 weeks as well. But everyone in the study will get the standard treatments that would normally be prescribed for Kawasaki disease. Which treatment children and young people get will be chosen by a computer.

A study doctor or nurse will come to see children and young people in the KD-CAAP study regularly while they are in hospital. They will take a small amount of extra blood for extra tests to look at how steroids might be helping patients. Some of this blood will also be used for genetic testing to try to work out why some children and young people get Kawasaki disease and others don’t. Children and young people will also have visits at the hospital or clinic 1,2,6 and 12 weeks after joining the study, for check-up visits to make sure everything is okay. A study doctor or nurse will do scans and tracing of the heart at these visits, and also blood and urine tests. At some assessments a study doctor or nurse will ask some questions about how things are going.