Kawasaki Disease Project
We propose here the “re-purposing” of atorvastatin to reduce pro-inflammatory host responses and improve cardiovascular outcome in children with acute Kawasaki disease (KD), a self-limited vasculitis that is the most common cause of acquired heart disease in children. Although high-dose intravenous immunoglobulin (IVIG) plus aspirin reduces the risk of coronary artery damage, 5-10% of children with KD will go on to develop coronary artery aneurysms that may result in myocardial ischemia, infarction, or death. Once aneurysms have formed, the damage to the arterial wall is irreversible and although myointimal proliferation can restore the lumen to a more normal caliber, these arteries are never normal and over time stenoses and calcification lead to ischemic complications.
Thus, the goal of treatment should be prevention or attenuation of coronary artery damage. Based on preliminary data from our laboratory, arterial damage in KD results from immune activation and vessel wall infiltration by myofibroblasts, neutrophils, and T-cells with secretion of pro-inflammatory cytokines, elastases, and matrix metalloproteinases (MMPs). The proposed, multicenter, blinded, placebo-controlled Phase III study will assess the efficacy on the attenuation of coronary artery abnormalities (Specific Aim 1) and anti-inflammatory and anti-oxidant effects (Specific Aim 2) of atorvastatin in acute KD.
This study will determine if atorvastatin could reduce the morbidity and mortality of acute KD. This University of California Biomedical Research Acceleration, Integration, & Development (UC BRAID) grant will fund the coordination of the necessary infrastructure to bring together the 5 UC campuses in order to apply to the NIH for an R01 to support a Phase III clinical trial.