ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)

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.

Inclusion Criteria:18 years or olderA diagnosis of ANCA-associated vasculitis that has been in remission for ≥6 months.The diagnosis of AAV will have been made in accordance with the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides criteria. Remission will be defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 for at least 2 months prior to the screening visit whilst taking prednisolone at daily dose ≤7.5mg, in conjunction with the treating clinician's assessment of clinically silent disease.eGFR ≥25ml/min/1.73m2 at screening.Women of childbearing potential, beginning at menarche, must agree to the use of one highly reliable method of contraception (ie, a failure rate of <1% per year) for at least 30 days prior to the first dose of the study medication (ie, for hormonal contraception) or according to manufacturer's recommendation (ie, for an intrauterine device) until 30 days after the last dose of the study medication, and must have a negative pregnancy test at screening. Women of childbearing potential are defined as those who are fertile, following menarche and until becoming postmenopausal, unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as amenorrhea for more than 24 consecutive months without an alternative medical cause; women on hormone replacement therapy must have a documented plasma follicle-stimulating hormone level >40 mIU/mL.Exclusion Criteria:Age <18 yearsActive vasculitisLiver diseaseUntreated hypertension (defined as systolic blood pressure >160 bpm and diastolic blood pressure >100 bpm)eGFR <25ml/min/1.73m2Any organ transplant recipientsHaemodialysis/peritoneal dialysis patientsA requirement for any medications contraindicated whilst taking sparsentanCongestive heart failurePatients not medically fit to attend for study visitsPatients without mental capacity or willingness to provide informed consentHistory of multiple and/or severe (clinical judgement as determined by the investigator) allergic reactions to drugs, including the study drug or food.Patients who are pregnant or breast feeding, or those who plan to become pregnant during the studyParticipation in another clinical trial for 28 days before or 90 days after the study period.