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

Not Applicable

Recruiting

• Conditions: High Risk Cardiovascular Disease; Hypertension; High Cardiovascular Risk
• Interventions: Drug: Zilebesiran; Drug: Placebo

• Registration Number: NCT07181109
• Lead Sponsor: Alnylam Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-12
• Study First Submitted QC: 2025-09-12
• Last Update Submitted: 2025-09-12
• Study First Posted: 2025-09-18
• Last Update Posted: 2025-09-18
• Study Start: 2025-10-24
• Primary Completion: 2030-10-29
• Study Completion: 2030-10-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 11000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Clinical Trial Site; 🇺🇸 Mesquite, Texas, United States