Non Inferiority KawasakI Trial With Anakinra

This is a multicenter national, open label, randomized, controlled, interventional trial followed by a long-term observational extension period. This is a non-inferiority study Patients who fulfill the eligibility criteria and whose parent/carer (legal representative) has provided informed consent will be randomized 1:1 to receive either

• IVIG 2g/kg administered in 10-12 hours as per local standard of care (standard treatment) OR
• Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day (investigational treatment)

PLUS Aspirin (ASA) 50mg/kg QID until 36 hours from fever disappearance, then switched to low-dose (3-5 mg/Kg once a day) as per standard of care

Inclusion criteria

• KD defined in at least one of the three following ways as per American Heart Association (AHA) criteria: Fever for at least 5 days in addition to 4 of the following 5 clinical criteria:

• bilateral non-purulent conjunctivitis
• cervical lymphadenopathy
• polymorphous skin rash
• changes in lips or mucosa (strawberry tongue, red cracked lips, diffuse erythematous oropharynx)
• extremity changes (erythema, oedema of palms and soles in initial phase, and at convalescent stage skin peeling)
• less than 5 days of fever but all 5 clinical criteria above
• incomplete KD cases defined as:

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

AND for both age groups, CRP ≥30 mg/L or erythrocyte sedimentation rate (ESR) ≥40 mm/hr (or both) AND for both age groups EITHER the presence of any 3 or more of: anaemia for age (haemoglobin < lower limit of normal reference range for local laboratory); platelet count ≥450,000/L or <140,000/L; albumin <30 g/L; elevated ALT (> upper limit of normal reference range for local laboratory); white cell count ≥15,000/L; urine ≥10 white blood cells per high power field iv.

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 (internal diameter 2≤Z<2.5; and not meeting the exclusion criteria for aneurysmal change as defined below).

• To be enrolled children need to show persistent fever ≤7 days
• Written informed consent from an appropriate legal representative(s), and assent from patients older than 7 years

Exclusion criteria

• Patients with KD and already established coronary artery aneurysms (CAA), as per AHA definition, at screening.
• Clinical picture consistent with Kawasaki Shock Syndrome (KDSS) or Macrophage Activation Syndrome (MAS) OR Multisystem Inflammatory Syndrome in Children (MIS-C)
• History or evidence of any previous heart disease
• Known hypersensitivity to anakinra, IVIG and ASA or any medical condition that contraindicates the use of these treatments
• Patients with KD receiving IVIG, corticosteroids, immunosuppressants, biologic treatments at the time of screening