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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034545-02
Application #
3347525
Study Section
Clinical Trials Review Committee (CLTR)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Moran, A M; Newburger, J W; Sanders, S P et al. (2000) Abnormal myocardial mechanics in Kawasaki disease: rapid response to gamma-globulin. Am Heart J 139:217-23
Beiser, A S; Takahashi, M; Baker, A L et al. (1998) A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol 81:1116-20
Burns, J C; Wright, J D; Newburger, J W et al. (1995) Conjunctival biopsy in patients with Kawasaki disease. Pediatr Pathol Lab Med 15:547-53
Finberg, R W; Newburger, J W; Mikati, M A et al. (1992) Effect of high doses of intravenously administered immune globulin on natural killer cell activity in peripheral blood. J Pediatr 120:376-80
Newburger, J W; Takahashi, M; Beiser, A S et al. (1991) A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324:1633-9
Newburger, J W; Burns, J C; Beiser, A S et al. (1991) Altered lipid profile after Kawasaki syndrome. Circulation 84:625-31
Koren, G; Silverman, E; Sundel, R et al. (1991) Decreased protein binding of salicylates in Kawasaki disease. J Pediatr 118:456-9
Ingelfinger, J R; Newburger, J W (1991) Spectrum of renal anomalies in patients with Williams syndrome. J Pediatr 119:771-3
Burns, J C; Mason, W H; Glode, M P et al. (1991) Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. United States Multicenter Kawasaki Disease Study Group. J Pediatr 118:680-6
Melish, M E; Hicks, R V (1990) Kawasaki syndrome: clinical features. Pathophysiology, etiology and therapy. J Rheumatol Suppl 24:2-10

Showing the most recent 10 out of 29 publications