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Zilebesiran in Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease

ZENITH: A Phase 3 Global, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Zilebesiran in Addition to Standard of Care in Reducing Major Adverse Cardiovascular Events in Adult Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease

Who can join

Ages 18 and older · All sexes

Inclusion Criteria:

* Is 18 years or older for patients with established cardiovascular disease (CVD)
* Is 55 years or older for patients with high risk for CVD
* Has established CVD (defined as coronary, cerebrovascular, or peripheral artery disease) or high risk for CVD
* Has treated hypertension on stable therapy with at least 2 standard of care antihypertensive medications, one of which must be a thiazide, thiazide-like, or loop diuretic

Exclusion Criteria:

* Has known history of secondary hypertension
* Has symptomatic orthostatic hypotension
* Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3×upper limit of normal (ULN)
* Has total serum bilirubin \>1.5×ULN
* Has international normalized ratio (INR) \>1.5
* Has serum potassium \>4.8 mEq/L
* Has estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m\^2

About the study

The purpose of this study is to evaluate whether zilebesiran versus placebo reduces the risk of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events. This is an event-driven study that will continue until the targeted number of positively adjudicated primary endpoint clinical outcome events (COEs) have been reached.

What is being tested

• Zilebesiran (drug)
• Placebo (drug)

Sponsor: Alnylam Pharmaceuticals · Participants: 11,000 · Started: Sep 22, 2025

Contact the study team

• Clinical Trial Information Line · Phone: 1-877-ALNYLAM
• Clinical Trial Information Line · Phone: 1-877-256-9526

Official record on ClinicalTrials.gov — NCT07181109

Locations in the U.S.

Conditions

• High Blood Pressure
• Cardiovascular Disease

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.