Prevention of Coronary Aneurysms in Kawasaki Syndrome
Summary
To test the efficacy of intravenous gamma globulin (IVGG) in preventing coronary artery aneurysms in children with Kawasaki Syndrome.
Description
BACKGROUND:
Kawasaki Syndrome is an acute febrile illness that occurs predominantly in previously healthy young children. It is of unknown etiology and was first described in Japan in 1967. The illness carries an acute mortality rate of approximately 3 percent. The Centers for Disease Control defines Kawasaki Syndrome as a fever lasting five or more days for which no explanation can be found. Patients also must have at least four of the following symptoms: bilateral conjunctival infection; infected or fissured lips, pharynx, or a 'strawberry tongue'; erythema of the palms or soles, or edema of the hands or feet, or generalized or periungual desquamation; rash; and cervical lymphadenopathy.
Coronary artery aneurysms occur in 15-20 percent of children with the illness. In the past, no treatment had been shown to be effective in preventing this complication. Investigators in Japan began to use IVGG to reduce the aneurysm formation. Preliminary results showing the usefulness of this therapy led to a multicenter trial in Japan in which 400 mg/kg/day of IVGG were given for five days to children also receiving aspirin for the condition. Results of the Japanese trial showed that within 29 days of the onset of the disease, coronary artery dilatation had developed in 42 percent of the aspirin-treated children and in 15 percent of the IVGG and aspirin-treated children.
DESIGN NARRATIVE:
Phase I was randomized, unblinded and stratified by age, sex, and center. Subjects were randomized to receive either 80 to 120 mg/kg/day of aspirin through day 14 of illness, subsequently reduced to 3 to 5 mg/kg/day as a single daily dose or to 400 mg/kg/day of intravenous gamma globulin for four consecutive days plus aspirin as above. Primary endpoint was formation of aneurysms as demonstrated by echocardiograms. Follow-up was for 7 weeks.
Phase II of the trial began enrollment of 549 patients in May 1986 and ended enrollment in November 1989. Two hundred and seventy six children were randomized to receive 400 mg/kg of intravenous gamma globulin over four consecutive days. Two hundred and seventy-three received a single infusion of 2 g/kg of body weight over 10 hours. Both treatment groups received 100 mg/kg of aspirin per day through day 14 and then 3 to 5 mg/kg per day. The primary outcome variables were the presence or absence of coronary artery abnormalities evident at the two week and seven week follow-up examinations. Echocardiograms were obtained for 523 children at the two week visit and for 520 children at the seven week visit.
Study Design
Allocation: Randomized, Intervention Model: Parallel Assignment, Primary Purpose: Prevention
Conditions
Cardiovascular Diseases
Intervention
immunoglobulins, intravenous, aspirin
Status
Completed
Source
National Heart, Lung, and Blood Institute (NHLBI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00000520
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Immunoglobulins, Intravenous
Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.
Sodium Salicylate
A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)
Asthma, Aspirin-induced
Asthmatic adverse reaction (e.g., BRONCHOCONSTRICTION) to conventional NSAIDS including aspirin use.
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.
Diagnostic Techniques, Cardiovascular
Methods and procedures for the diagnosis of diseases or dysfunction of the cardiovascular system or its organs or demonstration of their physiological processes.
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