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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

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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 Teilnehmende gesucht1.153 Studienzentren35 Länder

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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.

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.

Zusammenfassung

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.

Erkrankungen

  • High Risk Cardiovascular Disease
  • Hypertension
  • High Cardiovascular Risk

Eignung

Eignung
GeschlechtAlle
Alter18 YearsKein Höchstalter
Gesunde FreiwilligeNein

Eignung im Wortlaut des Registers

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

Eignung in einfachen Aussagen

Die Kriterien dieses Eintrags wurden noch nicht in einzelne Aussagen aufgeschlüsselt. Der Registertext oben ist vollständig und ist die maßgebliche Fassung.

Studiendesign

Studiendesign
StudientypInterventionell
PhasePhase 3
ZuteilungRandomisiert
InterventionsmodellPARALLEL
Primäres ZielTREATMENT
VerblindungQUADRUPLE (4)
Teilnahme11.000 Teilnehmende gesucht

Sponsor und Mitwirkende

  • Alnylam Pharmaceuticals Sponsor
  • Hoffmann-La Roche Mitwirkende

Studienarme und Interventionen

  • 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.

Interventionen

  • Arzneimittel Placebo

    Placebo will be administered SC

  • Arzneimittel Zilebesiran

    Zilebesiran will be administered SC

Endpunkte

  1. Primärer Endpunkt

    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)

    Zeitrahmen Up to approximately 5 years

  2. Sekundärer Endpunkt

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

    Zeitrahmen Baseline and Month 6

  3. Sekundärer Endpunkt

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

    Zeitrahmen Up to approximately 5 years

  4. Sekundärer Endpunkt

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

    Zeitrahmen Up to approximately 5 years

  5. Sekundärer Endpunkt

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

    Zeitrahmen Up to approximately 5 years

  6. Sekundärer Endpunkt

    Time to All-cause Death

    Zeitrahmen Up to approximately 5 years

Daten

Daten
Startdatum22. September 2025 (tatsächlich)
Primärer Abschluss23. September 2030 (geschätzt)
Abschluss23. September 2030 (geschätzt)
Erstveröffentlichung18. September 2025 (tatsächlich)
Zuletzt aktualisiert18. September 2026
Ergebnisse veröffentlichtIm Registereintrag nicht angegeben
Status zuletzt bestätigtSeptember 2026

Tatsächlich bedeutet, dass das Ereignis eingetreten ist. Geschätzt bedeutet, dass der Sponsor es erwartet. Die beiden bedeuten Unterschiedliches.

Standorte

922 Studienzentren rekrutieren

Argentina

Argentina
EinrichtungStadtBundesland oder RegionStatus
Clinical Trial SiteBahía BlancaRekrutiert
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Clinical Trial SiteBuenos AiresRekrutiert
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Clinical Trial SiteCiudadelaRekrutiert
Clinical Trial SiteCoronel SuárezRekrutiert
Clinical Trial SiteCorrientesRekrutiert
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Clinical Trial SiteGeneral San MartínRekrutiert
Clinical Trial SiteGranadero BaigorriaRekrutiert
Clinical Trial SiteLanús EsteRekrutiert
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Clinical Trial SiteMorónRekrutiert
Clinical Trial SiteQuilmesRekrutierung noch nicht begonnen
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Clinical Trial SiteRío CuartoRekrutiert

1.103 weitere Studienzentren sind im Registereintrag aufgeführt.

Studiendokumente

In diesem Registereintrag sind keine Dokumente verlinkt.

Änderungen im Zeitverlauf

  1. 18. September 2026

    Abschlussdatum nach vorne verschoben

    Primary completion advanced 7 days

    2030-09-302030-09-23

  2. 18. September 2026

    Studienzentrum hinzugefügt

    48 sites added (1153 total)

    11051153

  3. 19. August 2026

    Studienzentrum hinzugefügt

    110 sites added (1105 total)

    9951105