A Trial Comparing the Efficacy and Safety of Anakinra Versus Intravenous Immunoglobulin (IVIG) Retreatment, in Patients With Kawasaki Disease Who Failed to Respond to Initial Standard IVIG Treatment

Condition(s) studied

Investigational drug(s) / intervention(s)

ANAKINRA: The patients will receive anakinra, an analogue of the IL-1 receptor antagonist, at a starting dose of 4 mg/kg. If patients are still febrile with 12 hours (H12) of treatment, they will receive a supplementary dose of 2 mg/Kg; otherwise, they will remain at a starting dose of 4 mg/kg. If they are still febrile at H24, they will receive a dose of 8mg/kg; otherwise, they will maintain their dose of 6 mg/kg. Patients with temperature \<38°C at any point between initiation and day 14, but who develop secondary fever due to KD could have further escalation dose of anakinra until a maximum dose of 8mg/Kg. Patients will receive anakinra during 14 days independently of the period of escalation dose if any. After the last escalation dose, if any necessary, the primary criteria will be measured. Patients not responding to anakinra will follow usual standard care and will complete information related to all the study visits

Intravenous immunoglobulin: The patients will receive a standard therapy, IVIG infusion of 2g/kg, and their treatment will follow usual standard care. Patients in the IVIG treatment will complete information related to the study visits.

Study summary

Kawasaki disease (KD) is the most frequent vasculitis in younger children \<5years, and the first cause of acquired ischemic myocardiopathy in childhood. Exceptionally, KD may cause early death during the acute phase by myocardial infarction, but may compromise the long-term cardiovascular outcome by accelerating atherosclerotic disease.

The incidence of KD is high in far-Eastern countries and Hawaii but KD is relatively rare in other regions (10/100000 children \<5years in northern Europe) which makes it difficult to develop research on these rare population.

Early recognition and treatment by intravenous immunoglobulins (IVIG) influences the prognosis positively. IVIG are the standard of care and decrease significantly the risk of coronary aneurysms. However, despite a first infusion of IVIG, 20% of KD patients remain febrile and have high risk of coronary vasculitis. Recent Japanese research group assessed additional cyclosporine treatment in first line KD treatment but failed preventing relapse. To date there is no agreement for a more effective second line treatment.

Based on the auto-inflammatory pattern of KD, the investigators hypothesize that anti IL-1 blocking agents could bring a rapid and sustained effect on systemic and coronary inflammation in patients with KD.

Our hypotheses are:

1. Anakinra treatment may reduce the early and long-term mortality of patients with Kawasaki Disease (KD), by a rapid and sustained effect on vascular inflammation.
2. The safety of anakinra is good, as the drug has a very short half-life, which allows its rapid withdrawal in case of serious adverse event.

The use of anakinra is not associated with the risk of contamination by infectious agents, which remain even minimal, a possibility with the use of IVIG.

Eligibility

Primary outcome measure(s)

• Fever — 48 hours
  The main criterion-evaluating efficacy in both groups is: the patient must reach a body (axillary (+0.5°C), tympanic, oral) temperature \<38˚C within 2 days after initiation of treatment (i.e. a binary outcome: success/failure).

Trial sites (1)

On this site

More Assistance Publique - Hôpitaux de Paris trials in France

Other trials for the same condition