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
ZENITH: Reducing Cardiovascular Events in Hypertension Patients
Plain English Summary
Zilebesiran in Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease is a Phase 3 clinical trial sponsored by Alnylam Pharmaceuticals studying High Risk Cardiovascular Disease, Hypertension, High Cardiovascular Risk. Tests zilebesiran to reduce major cardiovascular events in adults with uncontrolled hypertension and high cardiovascular risk. For patients aged 18+ with established cardiovascular disease or 55+ with high risk, on stable antihypertensive medications. Participation involves taking zilebesiran or placebo injections every 6 months for up to 5 years. Alternatives include standard antihypertensive medications and lifestyle changes. The trial aims to enroll 11000 participants.
Official 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.
Who Can Participate
Here is what you need to know about eligibility for this trial. Ages 18+ for established CVD, 55+ for high risk CVD. Must have treated hypertension and be on stable therapy with at least 2 antihypertensive medications. Cannot have secondary hypertension, orthostatic hypotension, or certain liver or kidney issues. Must not have a history of secondary hypertension or specific liver or kidney conditions. This trial is studying High Risk Cardiovascular Disease, Hypertension, High Cardiovascular Risk, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.
What They're Measuring
The primary outcome measures the time to first occurrence of a composite endpoint of cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure, providing crucial data for patient care. The specific primary outcome measures are: 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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.
Why This Trial Matters
This trial aims to fill a gap in treating high-risk cardiovascular events in patients with uncontrolled hypertension, offering a new approach beyond current medications. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets High Risk Cardiovascular Disease, Hypertension, High Cardiovascular Risk, where improved treatment options are needed.
Investor Insight
With a large market size and competitive landscape, this trial has a high probability of approval, making it an attractive investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 11000 participants suggests significant investment in this program.
Is This Trial Right for Me?
Ask your doctor if you have established cardiovascular disease or are at high risk. Participation involves regular check-ups and taking zilebesiran or placebo injections every 6 months. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: RANDOMIZED
- Model: PARALLEL
- Masking: QUADRUPLE
- Enrollment: 11,000 participants
Interventions
- DRUG: Zilebesiran — Zilebesiran will be administered SC
- DRUG: Placebo — Placebo will be administered SC
Primary Outcomes
- 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 Outcomes
- 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)
Full Eligibility Criteria
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
Trial Locations
- Clinical Trial Site, Huntsville, Alabama, United States
- Clinical Trial Site, Huntsville, Alabama, United States
- Clinical Trial Site, Sheffield, Alabama, United States
- Clinical Trial Site, Chandler, Arizona, United States
- Clinical Trial Site, Gilbert, Arizona, United States
- Clinical Trial Site, Glendale, Arizona, United States
- Clinical Trial Site, Mesa, Arizona, United States
- Clinical Trial Site, Phoenix, Arizona, United States
- Clinical Trial Site, Phoenix, Arizona, United States
- Clinical Trial Site, Sun City West, Arizona, United States
- ...and 10 more locations
Frequently Asked Questions
What is clinical trial NCT07181109?
NCT07181109 is a Phase 3 INTERVENTIONAL study titled "Zilebesiran in Patients With Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease." It is currently recruiting and is sponsored by Alnylam Pharmaceuticals. The trial targets enrollment of 11000 participants.
What conditions does NCT07181109 study?
This trial investigates treatments for High Risk Cardiovascular Disease, Hypertension, High Cardiovascular Risk. The primary condition under study is High Risk Cardiovascular Disease.
What treatments are being tested in NCT07181109?
The interventions being studied include: Zilebesiran (DRUG), Placebo (DRUG). Zilebesiran will be administered SC
What does Phase 3 mean for NCT07181109?
Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.
What is the current status of NCT07181109?
This trial is currently "Recruiting." It started on 2025-09-22. The estimated completion date is 2030-09-30.
Who is sponsoring NCT07181109?
NCT07181109 is sponsored by Alnylam Pharmaceuticals. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT07181109?
The trial aims to enroll 11000 participants. The trial is currently recruiting and accepting new participants.
How is NCT07181109 designed?
This is a interventional study, uses randomized allocation, follows a parallel design, employs quadruple masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.
What are the primary outcomes being measured in NCT07181109?
The primary outcome measures are: 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). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT07181109 being conducted?
This trial is being conducted at 20 sites, including Huntsville, Alabama; Sheffield, Alabama; Chandler, Arizona; Gilbert, Arizona and 16 more sites (United States).
Where can I find official information about NCT07181109?
The official record for NCT07181109 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT07181109. This government database provides the most up-to-date and detailed information about the trial.
What is NCT07181109 testing in simple terms?
Tests zilebesiran to reduce major cardiovascular events in adults with uncontrolled hypertension and high cardiovascular risk. For patients aged 18+ with established cardiovascular disease or 55+ with high risk, on stable antihypertensive medications.
Why is this trial significant?
This trial aims to fill a gap in treating high-risk cardiovascular events in patients with uncontrolled hypertension, offering a new approach beyond current medications. As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.
What are the potential risks of participating in NCT07181109?
Potential side effects include injection site reactions, headache, and fatigue. Monitor for any unusual symptoms and report them to your doctor. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT07181109?
Ask your doctor if you have established cardiovascular disease or are at high risk. Participation involves regular check-ups and taking zilebesiran or placebo injections every 6 months. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT07181109 signal from an investment perspective?
With a large market size and competitive landscape, this trial has a high probability of approval, making it an attractive investment opportunity. This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.
What happens if the treatment in this trial doesn't work?
Participation involves taking zilebesiran or placebo injections every 6 months for up to 5 years. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
Related Conditions
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.