ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)

Sponsor
University of Edinburgh
Study ID
NCT05630612
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • ANCA Associated Vasculitis
  • Cardiovascular Diseases
  • Kidney Diseases

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Sparsentan — DRUG
    6 weeks of treatment with sparsentan or irbesartan. This will be administered in a double-blind fashion.

Study Details

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.

Key Dates

Start date
Dec 8, 2022
Status verified
Aug 2025
Primary completion
Jul 18, 2024
Completion
Sep 1, 2027

Study Design

Enrollment
32 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Sparsentan
    20 participants with ANCA-associated vasculitis in long-term disease remission. Participants will undergo a forearm blood flow study where forearm vasodilatation will be assessed in response to acetylcholine (7.5, 15 and 30ug/min) and sodium nitroprusside (1, 2 and 4ug/min). Participants will also receive bradykinin (100, 300 and 1000pmol/min) in order to assess tPA release to measure fibrinolytic capacity. Participants will also have 24h blood pressure assessed as well as measurements of arterial stiffness, systemic haemodynamics and measures of urinary protein. After these baseline measures have been obtained the subject will receive 6 weeks of sparsentan. Finally the subject will undergo the same investigations listed above and we will compare to see if measurements obtained differ after treatment.
  • Active Comparator: Irbesartan
    20 participants with ANCA-associated vasculitis in long-term disease remission. Participants will undergo a forearm blood flow study where forearm vasodilatation will be assessed in response to acetylcholine (7.5, 15 and 30ug/min) and sodium nitroprusside (1, 2 and 4ug/min). Participants will also receive bradykinin (100, 300 and 1000pmol/min) in order to assess tPA release to measure fibrinolytic capacity. Participants will also have 24h blood pressure assessed as well as measurements of arterial stiffness, systemic haemodynamics and measures of urinary protein. After these baseline measures have been obtained the subject will receive 6 weeks of irbesartan. Finally the subject will undergo the same investigations listed above and we will compare to see if measurements obtained differ after treatment.

Primary Outcome Measure

Forearm blood flow [ Time Frame: Comparing baseline to after 6 weeks of intervention. ]

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