NCT07181109ClinicalTrials.gov

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

RecruitingTaking participants now, according to the registry record.

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In brief

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…

Phase 311,000 participants sought1,153 sites35 countries

Registered in 1 registry

ClinicalTrials.govNCT07181109Open this record at ClinicalTrials.govSynced 2 days ago

One study can be registered in several registries. We show it once and link every record we hold.

Trial information is shown as published by the registry, in its original language.

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2025-09-18; recorded start 2025-09-22
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Present: Uses blinding (masking)A masking level is recorded in the record
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 50 other studies in this databaseCounted from the lead sponsor named in the record (Alnylam Pharmaceuticals)
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 3 conditions.
Lead sponsor type recorded as: industry.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourDEFINITIVE

A definitive-grade design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding20/20
Quadruple-blind
Control arm13/15
Placebo / sham control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type10/10
Mortality / MACE endpoint (hard clinical outcome)
Multi-centre8/8
Multi-centre: 995 sites
Data monitoring committee7/7
A data monitoring committee is in place
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleMEGA

A very large study, international in scope: 11,000 participants (target), run at 1,153 sites, across 35 countries.

How this score is built

Enrolment38/40
11,000 participants (target)
Site count25/25
995 sites
Country count15/15
34 countries
Planned duration10/10
Planned over about 61 months
Sponsor scale6/10
Alnylam Pharmaceuticals has led 53 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Summary

Conditions

High Risk Cardiovascular Disease
Hypertension
High Cardiovascular Risk

Eligibility

Eligibility
Sex	All
Ages	18 Years – No maximum
Healthy volunteers	No

Eligibility as written in the registry

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

Eligibility in plain statements

This record's criteria have not been broken into separate statements yet. The registry text above is complete and is the authoritative version.

Study design

Study design
Study type	Interventional
Phase	Phase 3
Allocation	Randomised
Intervention model	PARALLEL
Primary purpose	TREATMENT
Masking	QUADRUPLE (4)
Enrolment	11,000 participants sought

Sponsor and collaborators

Alnylam Pharmaceuticals Sponsor
Hoffmann-La Roche Collaborators

Arms and interventions

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

Interventions

Drug Placebo
Placebo will be administered SC
Drug Zilebesiran
Zilebesiran will be administered SC

Outcome measures

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

Dates

Dates
Start date	September 22, 2025 (actual)
Primary completion	September 23, 2030 (estimated)
Completion	September 23, 2030 (estimated)
First posted	September 18, 2025 (actual)
Last updated	September 18, 2026
Results posted	Not stated in the registry record
Status last verified	September 2026

Actual means the event happened. Estimated means the sponsor expects it. The two mean different things.

Locations

922 sites are recruiting

Argentina

Argentina
Facility	City	Status
Clinical Trial Site	Bahía Blanca	Recruiting
Clinical Trial Site	Bahía Blanca	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Not yet recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Buenos Aires	Recruiting
Clinical Trial Site	Ciudadela	Recruiting
Clinical Trial Site	Coronel Suárez	Recruiting
Clinical Trial Site	Corrientes	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Córdoba	Recruiting
Clinical Trial Site	Esperanza	Recruiting
Clinical Trial Site	Formosa	Recruiting
Clinical Trial Site	General San Martín	Recruiting
Clinical Trial Site	Granadero Baigorria	Recruiting
Clinical Trial Site	Lanús Este	Recruiting
Clinical Trial Site	Mar del Plata	Recruiting
Clinical Trial Site	Mar del Plata	Recruiting
Clinical Trial Site	Morón	Recruiting
Clinical Trial Site	Quilmes	Not yet recruiting
Clinical Trial Site	Ramos Mejía	Recruiting
Clinical Trial Site	Rosario	Not yet recruiting
Clinical Trial Site	Rosario	Recruiting
Clinical Trial Site	Rosario	Recruiting
Clinical Trial Site	Rosario	Recruiting
Clinical Trial Site	Rosario	Recruiting
Clinical Trial Site	Rosario	Recruiting
Clinical Trial Site	Rosario	Recruiting
Clinical Trial Site	Río Cuarto	Recruiting

1,103 further sites are listed in the registry record.

Study documents

No documents are linked in this registry record.

Changes over time

September 18, 2026
Completion date moved earlier
Primary completion advanced 7 days
2030-09-302030-09-23
September 18, 2026
Site added
48 sites added (1153 total)
11051153
August 19, 2026
Site added
110 sites added (1105 total)
9951105

Registry: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT07181109

Categories

Registered in 1 registry

Interested in this study?

How this study is set up

Summary

Conditions

Eligibility

Eligibility as written in the registry

Eligibility in plain statements

Study design

Sponsor and collaborators

Arms and interventions

Interventions

Outcome measures

Dates

Locations

Argentina

Study documents

Changes over time