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

NCT07181109
clinicaltrials.gov
Phase
Phase 3
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Recruitment status
Recruiting
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Participants
11,000
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Lead sponsor
Alnylam Pharmaceuticals
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Start date
2025-09-22
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Number of sites
1,105
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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.
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Acronym
ZENITH
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Short title
Zilebesiran in Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease
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Official title
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
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2030-09-30
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First posted
2025-09-18
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Registry last updated
2026-08-19
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Primary completion date
2030-09-30
clinicaltrials.gov
Start date
2025-09-22
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Participants
11,000
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Participant count basis
Estimated
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Planned participants
11,000
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Protocol amendments
0
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Number of sites
1,105
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Alnylam Pharmaceuticals
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Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT07181109
clinicaltrials.gov
ClinicalTrials.gov ID
NCT07181109
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. 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)

    Timeframe: Up to approximately 5 years

  1. Change from Baseline in Mean Seated Office Systolic Blood Pressure (SBP) at Month 6

    Timeframe: Baseline and Month 6

  2. Time to First Occurrence of a Composite Endpoint of CV Death, Nonfatal MI, or Nonfatal Stroke

    Timeframe: Up to approximately 5 years

  3. Composite Endpoint of CV Death and Total (First and Subsequent) HF Events (Hospitalization for HF or Urgent HF Visit)

    Timeframe: Up to approximately 5 years

  4. Time to First Occurrence of Composite Endpoint of CV death, Nonfatal MI, Nonfatal Stroke, or Coronary Revascularization

    Timeframe: Up to approximately 5 years

  5. Time to All-cause Death

    Timeframe: Up to approximately 5 years

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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
Sources for eligibility
clinicaltrials.gov

  • Clinical Trial SiteBirmingham, United StatesRecruiting
  • Clinical Trial SiteBirmingham, United StatesNot yet recruiting
  • Clinical Trial SiteBirmingham, United StatesRecruiting
  • Clinical Trial SiteFairhope, United StatesRecruiting
  • Clinical Trial SiteFoley, United StatesRecruiting
  • Clinical Trial SiteHuntsville, United StatesNot yet recruiting
  • Clinical Trial SiteHuntsville, United StatesRecruiting
  • Clinical Trial SiteSheffield, United StatesRecruiting
  • Clinical Trial SiteChandler, United StatesRecruiting
  • Clinical Trial SiteGilbert, United StatesRecruiting
  • Clinical Trial SiteGlendale, United StatesNot yet recruiting
  • Clinical Trial SiteMesa, United StatesRecruiting
  • Clinical Trial SitePhoenix, United StatesRecruiting
  • Clinical Trial SitePhoenix, United StatesRecruiting
  • Clinical Trial SiteSun City, United StatesRecruiting
  • Clinical Trial SiteSun City West, United StatesRecruiting
  • Clinical Trial SiteTempe, United StatesRecruiting
  • Clinical Trial SiteTucson, United StatesRecruiting
  • Clinical Trial SiteTucson, United StatesRecruiting
  • Clinical Trial SiteTucson, United StatesNot yet recruiting
  • Clinical Trial SiteYuma, United StatesRecruiting
  • Clinical Trial SiteLittle Rock, United StatesRecruiting
  • Clinical Trial SiteLittle Rock, United StatesNot yet recruiting
  • Clinical Trial SiteLittle Rock, United StatesRecruiting
  • Clinical Trial SiteBeverly Hills, United StatesRecruiting

And 1,080 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-522960-34-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Collaborators (1)

Lead sponsors (1)

Conditions (1)