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

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07181109

Acronym

ZENITH

Enrollment

11000

Registered

2025-09-18

Start date

2025-09-22

Completion date

2030-09-30

Last updated

2026-08-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

High Cardiovascular Risk, High Risk Cardiovascular Disease, Hypertension

Keywords

High blood pressure, siRNA, Angiotensinogen, AGT, Cardiovascular disease, Uncontrolled hypertension, RNAi

Brief summary

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.

Interventions

DRUGZilebesiran

Zilebesiran will be administered SC

DRUGPlacebo

Placebo will be administered SC

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Time to First Occurrence of a Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Heart Failure (HF) Event (Hospitalization for HF or Urgent HF Visit)	Up to approximately 5 years

Secondary

Measure	Time frame
Change from Baseline in Mean Seated Office Systolic Blood Pressure (SBP) at Month 6	Baseline and Month 6
Time to First Occurrence of a Composite Endpoint of CV Death, Nonfatal MI, or Nonfatal Stroke	Up to approximately 5 years
Composite Endpoint of CV Death and Total (First and Subsequent) HF Events (Hospitalization for HF or Urgent HF Visit)	Up to approximately 5 years
Time to First Occurrence of Composite Endpoint of CV death, Nonfatal MI, Nonfatal Stroke, or Coronary Revascularization	Up to approximately 5 years
Time to All-cause Death	Up to approximately 5 years

Countries

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, India, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Romania, Serbia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States

Contacts

CONTACTClinical Trial Information Line

clinicaltrials@alnylam.com1-877-ALNYLAM

STUDY_DIRECTORMedical Director

Alnylam Pharmaceuticals

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 20, 2026