Zenith: Zilebesiran in Patients with Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease (NCT07181109)

Study ALN-AGT01-008 (ZilebEsiraN CardIovascular OuTcome Study in Hypertension [ZENITH]) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study designed to evaluate the efficacy and safety of zilebesiran, administered subcutaneously (SC), in adult patients with established CVD or high risk for CVD whose hypertension is not adequately controlled by at least 2 standard of care antihypertensive medications.  The primary objective of the study is to evaluate the efficacy of zilebesiran in patients with uncontrolled hypertension and with either established CVD or high risk for CVD by demonstrating the ability of zilebesiran to reduce the risk of CV death, nonfatal MI, nonfatal stroke, or HF events (hospitalization for HF or urgent HF visit). Secondary and exploratory objectives of the study include evaluating the effect of zilebesiran on additional clinical outcomes, blood pressure, and renal function. 

Trial phase

Phase 3

Trial participation type

This trial has been designed for the Clinical Research of a Drug.

Principal investigator

A/Prof James Shaw

Key inclusion data

This study will include adults (≥18 years of age for patients with established CVD and ≥55 years  of age for patients with high risk for CVD at the time of initial informed consent) with treated  hypertension (office SBP ≥140 mmHg to <180 mmHg) on stable therapy with at least 2 standard  of care antihypertensive medications, one of which must be a thiazide, thiazide-like, or loop  diuretic, and with either established CVD (defined as coronary, erebrovascular, or peripheral artery disease) or with high risk for CVD. Patients with secondary hypertension, symptomatic orthostatic hypotension, or serum potassium >4.8 mEq/L will be excluded.