Kawasaki Syndrome is an acute febrile illness of unknown etiology with an incidence reaching as high as 179/100,000 in epidemic periods. The case-fatality ratio is 0.5-2.8%, with virtually all deaths occurring secondary to its cardiac sequelae. Coronary artery aneurysms occur in 15-20% of children. Conventional therapy consists of aspirin to inhibit platelet aggregation in hope of preventing occlusion of the coronary arteries. Recent uncontrolled studies in Japan using intravenous gamma globulin therapy have shown a dramatic decrease in the incidence of aneurysms and the duration of fever. Preliminary results from the present investigators show a similarly promising effect. The proposed study will compare the effect of intravenous gamma globulin plus aspirin therapy versus aspirin alone with respect to: (1) the occurrence of coronary artery aneurysms, and (2) severity of clinical course as measured by number of days of fever and rate of fall in acute phase reactants.
These aims will be achieved through a multi-center, collaborative, prospective, randomized, open (unblinded) therapeutic trial, with randomization stratified by age, sex, and center. To be eligible for participation in the study, subjects must meet the Center for Disease Control criteria for Kawasaki Syndrome, with exclusion of children who present to the participating centers after the tenth day of illness. We anticipate an enrollment of 100 to 150 subjects per year. Children will be randomized to receive either (1) aspirin 80 to 120 mg/kg/day through Day 14 of illness, subsequently reduced to 3 to 5 mg/kg/day as a single daily dose, or (2) intravenous gamma globulin 400 mg/kg/day for four consecutive days plus aspirin as above. The primary outcome of interest is formation of aneurysms, as monitored by echocardiograms. Two dimensional echoes will be performed with standardized technique and will be interpreted centrally with reviewers blinded to therapy group. Analysis of results will include multivariate techniques to determine which variables relate to occurrence of aneurysms and then to determine an adjusted effect of treatment intervention. We believe this study will help resolve an important issue. If negative, it will prevent the widespread unnecessary use of an extremely expensive form of therapy. If positive, it will provide a strong indication for the use of intravenous gamma globulin to prevent the cardiac sequelae of Kawasaki Syndrome, a problem for which no current treatment has proven efficacy.
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