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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

En recrutementAccepte des participants actuellement, selon la fiche du registre.
Contacter cette étude

En bref

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 recherchés1 153 sites35 pays

Catégories

Enregistré dans 1 registre

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Les informations de l'essai sont affichées telles que publiées par le registre, dans leur langue d'origine.

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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.

Résumé

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.

Affections

  • High Risk Cardiovascular Disease
  • Hypertension
  • High Cardiovascular Risk

Éligibilité

Éligibilité
SexeTous
Âges18 YearsAucun maximum
Volontaires sainsNon

Éligibilité telle qu'elle figure dans le registre

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

Éligibilité en énoncés simples

Les critères de cette fiche n'ont pas encore été décomposés en énoncés distincts. Le texte du registre ci-dessus est complet et fait foi.

Conception de l'étude

Conception de l'étude
Type d'étudeInterventionnelle
PhasePhase 3
RépartitionRandomisée
Modèle d'interventionPARALLEL
Objectif principalTREATMENT
InsuQUADRUPLE (4)
Recrutement11 000 participants recherchés

Promoteur et collaborateurs

  • Alnylam Pharmaceuticals Promoteur
  • Hoffmann-La Roche Collaborateurs

Groupes et 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

  • Médicament Placebo

    Placebo will be administered SC

  • Médicament Zilebesiran

    Zilebesiran will be administered SC

Critères de jugement

  1. Critère de jugement principal

    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)

    Délai Up to approximately 5 years

  2. Critère de jugement secondaire

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

    Délai Baseline and Month 6

  3. Critère de jugement secondaire

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

    Délai Up to approximately 5 years

  4. Critère de jugement secondaire

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

    Délai Up to approximately 5 years

  5. Critère de jugement secondaire

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

    Délai Up to approximately 5 years

  6. Critère de jugement secondaire

    Time to All-cause Death

    Délai Up to approximately 5 years

Dates

Dates
Date de début22 septembre 2025 (réelle)
Achèvement principal23 septembre 2030 (estimée)
Achèvement23 septembre 2030 (estimée)
Première publication18 septembre 2025 (réelle)
Dernière mise à jour18 septembre 2026
Résultats publiésNon précisé dans la fiche du registre
Statut vérifié pour la dernière foisseptembre 2026

Réelle signifie que l'événement a eu lieu. Estimée signifie que le promoteur s'y attend. Les deux ont un sens différent.

Lieux

922 sites sont en recrutement

Argentina

Argentina
ÉtablissementVilleÉtat ou régionStatut
Clinical Trial SiteBahía BlancaEn recrutement
Clinical Trial SiteBahía BlancaEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
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Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresPas encore en recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteBuenos AiresEn recrutement
Clinical Trial SiteCiudadelaEn recrutement
Clinical Trial SiteCoronel SuárezEn recrutement
Clinical Trial SiteCorrientesEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteCórdobaEn recrutement
Clinical Trial SiteEsperanzaEn recrutement
Clinical Trial SiteFormosaEn recrutement
Clinical Trial SiteGeneral San MartínEn recrutement
Clinical Trial SiteGranadero BaigorriaEn recrutement
Clinical Trial SiteLanús EsteEn recrutement
Clinical Trial SiteMar del PlataEn recrutement
Clinical Trial SiteMar del PlataEn recrutement
Clinical Trial SiteMorónEn recrutement
Clinical Trial SiteQuilmesPas encore en recrutement
Clinical Trial SiteRamos MejíaEn recrutement
Clinical Trial SiteRosarioPas encore en recrutement
Clinical Trial SiteRosarioEn recrutement
Clinical Trial SiteRosarioEn recrutement
Clinical Trial SiteRosarioEn recrutement
Clinical Trial SiteRosarioEn recrutement
Clinical Trial SiteRosarioEn recrutement
Clinical Trial SiteRosarioEn recrutement
Clinical Trial SiteRío CuartoEn recrutement

1 103 sites supplémentaires sont indiqués dans la fiche du registre.

Documents de l'étude

Aucun document n'est lié dans cette fiche du registre.

Évolution au fil du temps

  1. 18 septembre 2026

    Date d'achèvement avancée

    Primary completion advanced 7 days

    2030-09-302030-09-23

  2. 18 septembre 2026

    Site ajouté

    48 sites added (1153 total)

    11051153

  3. 19 août 2026

    Site ajouté

    110 sites added (1105 total)

    9951105