ZENITH: Zilebesiran to Reduce Major Adverse Cardiovascular Events
Research type
Research Study
Full 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
IRAS ID
1012767
Contact name
Emily Cubbon
Contact email
Sponsor organisation
Alnylam Pharmaceuticals, Inc
Clinicaltrials.gov Identifier
Research summary
Researchers aim to evaluate the safety and efficacy of zilebesiran, a new medication for hypertension and cardiovascular disease, when used alongside standard treatments. Hypertension, characterised by excessive pressure on artery walls, can lead to severe cardiovascular issues if uncontrolled, even with current medications and lifestyle changes. Zilebesiran targets the liver-produced protein angiotensinogen (AGT), which contributes to high blood pressure and related diseases.
The study's primary goal is to determine if zilebesiran reduces serious cardiovascular events compared to a placebo. Secondary goals include assessing its impact on blood pressure after six months, its effect on individual cardiovascular issues, and its influence on overall mortality rates.
Approximately 11,000 participants with cardiovascular disease or high-risk profiles for cardiovascular disease will be enrolled. Eligible participants must be 18 or older (55 or older for high-risk individuals), have high blood pressure, and be on at least two hypertension medications, including a diuretic. Exclusions include hypertension from other conditions, orthostatic hypotension, or high blood potassium levels.
The study involves a double-blind treatment period where neither participants nor doctors know who receives zilebesiran or placebo. Participants will continue their standard hypertension treatments while receiving injections of zilebesiran or placebo every six months. The study will last 2.5 to 5 years, ending once a predetermined number of cardiovascular events occur.
Potential benefits include lowered blood pressure and reduced cardiovascular risks, while risks involve liver function abnormalities, injection site reactions, low blood pressure, high blood potassium, kidney issues, and angioedema. Detailed information is provided in the study protocol.
REC name
London - Chelsea Research Ethics Committee
REC reference
25/LO/0751
Date of REC Opinion
18 Nov 2025
REC opinion
Further Information Favourable Opinion