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

ZENITH: A Phase 3 Global, Randomized, Double-blind, Placebocontrolled 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 - ZENITH

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

JPRN

Registry ID

JPRN-jRCT2051250137

Enrollment

450

Registered

2025-10-24

Start date

2025-10-31

Completion date

Unknown

Last updated

2026-06-29

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

Conditions

Hypertension not adequately controlled and with either established CVD or high risk for CVD

Interventions

Participants will be administered 300 mg zilebesiran or placebo subcutaneously (SC) once every 6 months as add-on therapy to their standard of care antihypertensive medications.

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Is 18 years or older for patients with established cardiovascular disease (CVD) 2.Is 55 years or older for patients with high risk for CVD 3.Has established CVD (defined as coronary, cerebrovascular, or peripheral artery disease) or high risk for CVD 4.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

Exclusion criteria: 1.Has known history of secondary hypertension 2.Has symptomatic orthostatic hypotension 3.Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) 4.Has total serum bilirubin > 1.5 x ULN 5.Has international normalized ratio (INR) > 1.5 6.Has serum potassium > 4.8 mEq/L 7.Has estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2

Design outcomes

Primary

Measure	Time frame
To evaluate whether zilebesiran versus placebo reduces the risk of CV death, nonfatal MI, nonfatal stroke, or HF events	—

Secondary

Measure	Time frame
To evaluate whether zilebesiran versus placebo reduces mean seated office SBP To evaluate whether zilebesiran versus placebo reduces the risk of nonfatal CV events and CV mortality To evaluate whether zilebesiran versus placebo reduces the risk of all-cause mortality	—

Countries

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hungary, India, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Serbia, Slovakia, South Africa, South Korea, Spain, Sweden

Contacts

Public ContactYasuko Otsuka

PPD-SNBL K.K.

yasuko.otsuka@thermofisher.com+81-80-9024-3956

Outcome results

None listed

Source: JPRN (via WHO ICTRP) · Data processed: Jul 3, 2026