ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)

Summary

ANCA-associated vasculitis is an autoimmune disease that causes damage to blood vessels. This leads to organ damage with the number of organs affected and the severity of damage varying significantly between patients. Vasculitis patients also have a very high risk of heart attacks and strokes, called cardiovascular disease. A chemical called 'endothelin', produced by the blood vessels, causes vessels to stiffen and raises blood pressure and this associates with cardiovascular risk. The investigators have previously shown that by blocking the effects of endothelin you reduce vessel stiffness, lower blood pressure and improve vessel function. However, these studies only blocked endothelin for a few hours. Now, the investigators would like to see if it is possible to maintain these benefits by blocking endothelin for longer. Sparsentan is a tablet that blocks endothelin and lowers blood pressure. The investigators plan to give sparsentan to patients with vasculitis for 6 weeks. To determine if any beneficial effects of sparsentan are due to blood pressure lowering the investigators will give another group of vasculitis patients a tablet called irbesartan which lowers blood pressure but does not block endothelin. The investigators will compare the results between the two groups.

Timeline

Start

2022-12-08

Primary completion

2024-07-18

Completion

2027-09-01

Publications

• Background Farrah TE, Melville V, Czopek A, Fok H, Bruce L, Mills NL, Bailey MA, Webb DJ, Dear JW, Dhaun N. Arterial stiffness, endothelial dysfunction and impaired fibrinolysis are pathogenic mechanisms contributing to cardiovascular risk in ANCA-associated vasculitis. Kidney Int. 2022 Nov;102(5):1115-1126. doi: 10.1016/j.kint.2022.07.026. Epub 2022 Aug 20.

Drugs

Indications