Zilebesiran as Add-on Therapy in Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications (KARDIA-3)
KARDIA-3
A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Adult Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications
1 other identifier
interventional
375
6 countries
195
Brief Summary
The purpose of this study is to evaluate the effect of zilebesiran as add-on therapy in patients with high cardiovascular risk and hypertension not adequately controlled by standard of care antihypertensive medications.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2024
195 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 15, 2024
CompletedFirst Posted
Study publicly available on registry
February 22, 2024
CompletedStudy Start
First participant enrolled
February 29, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 19, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2025
CompletedMarch 2, 2026
February 1, 2026
1.3 years
February 15, 2024
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change from Baseline at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP)
Baseline and Month 3
Secondary Outcomes (9)
Change from Baseline at Month 3 in 24-Hour Mean SBP Assessed by Ambulatory Blood Pressure Monitoring (ABPM)
Baseline and Month 3
Change from Baseline at Month 6 in Mean Seated Office SBP
Baseline and Month 6
Change from Baseline at Month 6 in 24-Hour Mean SBP Assessed by ABPM
Baseline and Month 6
Proportion of Patients with Mean Seated Office SBP <140 mmHg and/or Reduction ≥10 mmHg without Intensification of Antihypertensive Regimen at Month 6
Month 6
Proportion of Patients with 24-hour Mean SBP assessed by ABPM <130 mmHg and/or Reduction ≥10 mmHg without Intensification of Antihypertensive Regimen at Month 6
Month 6
- +4 more secondary outcomes
Study Arms (2)
Zilebesiran
EXPERIMENTALParticipants will receive zilebesiran on Day 1 of the 6-month double-blind (DB) treatment period. Participants must be on stable doses of at least 2, but not more than 4, antihypertensive medications for at least 30 days prior to screening and plan to remain on stable doses of these medications during screening and through the DB treatment period.
Placebo
PLACEBO COMPARATORParticipants will receive placebo on Day 1 of the 6-month DB treatment period. Participants must be on stable doses of at least 2, but not more than 4, antihypertensive medications for at least 30 days prior to screening and plan to remain on stable doses of these medications during screening and through the DB treatment period.
Interventions
Zilebesiran administered by subcutaneous (SC) injection
Eligibility Criteria
You may qualify if:
- History of cardiovascular (CV) disease, high CV risk, or estimated glomerular filtration rate (eGFR) ≥30 to \<60 mL/min/1.73m\^2
- Mean seated office SBP ≥140 mmHg and ≤170 mmHg
- hour mean SBP ≥130 mmHg and ≤170 mmHg assessed by ABPM
- Must be on stable therapy with 2 to 4 classes of antihypertensive medications
You may not qualify if:
- Secondary hypertension
- Orthostatic hypotension
- Proteinuria \>3 g/day
- Serum potassium \>4.8 milliequivalents per liter (mEq/L)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (195)
Clinical Trial Site
Alexander City, Alabama, 35010, United States
Clinical Trial Site
Daphne, Alabama, 36526, United States
Clinical Trial Site
Foley, Alabama, 36535, United States
Clinical Trial Site
Huntsville, Alabama, 35801, United States
Clinical Trial Site
Huntsville, Alabama, 35805, United States
Clinical Trial Site
Montgomery, Alabama, 36117, United States
Clinical Trial Site
Gilbert, Arizona, 85297, United States
Clinical Trial Site
Phoenix, Arizona, 85028, United States
Clinical Trial Site
Sun City, Arizona, 85351, United States
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Tempe, Arizona, 85281, United States
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Tucson, Arizona, 85741, United States
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Beverly Hills, California, 90211, United States
Clinical Trial Site
Covina, California, 91723, United States
Clinical Trial Site
Encinitas, California, 92024, United States
Clinical Trial Site
Garden Grove, California, 92844, United States
Clinical Trial Site
Huntington Beach, California, 92647, United States
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Los Angeles, California, 90022, United States
Clinical Trial Site
Los Angeles, California, 90057, United States
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Northridge, California, 91324, United States
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Northridge, California, 91325, United States
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Pasadena, California, 91105, United States
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San Diego, California, 92108, United States
Clinical Trial Site
San Diego, California, 92111, United States
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San Dimas, California, 91773, United States
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Simi Valley, California, 93065, United States
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Vacaville, California, 95687, United States
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Van Nuys, California, 91405, United States
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West Hills, California, 91307, United States
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Colorado Springs, Colorado, 80918, United States
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Denver, Colorado, 80210, United States
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Denver, Colorado, 80230, United States
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Hartford, Connecticut, 06112, United States
Clinical Trial Site
Middlebury, Connecticut, 06762, United States
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Waterbury, Connecticut, 06708, United States
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Washington D.C., District of Columbia, 20009, United States
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Clearwater, Florida, 33756, United States
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Coral Gables, Florida, 33134, United States
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Daytona Beach, Florida, 32117, United States
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Fort Myers, Florida, 33912, United States
Clinical Trial Site
Hollywood, Florida, 33021, United States
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Jacksonville, Florida, 32204, United States
Clinical Trial Site
Jacksonville, Florida, 32209, United States
Clinical Trial Site
Jacksonville, Florida, 32256, United States
Clinical Trial Site
Jensen Beach, Florida, 34957, United States
Clinical Trial Site
Lake City, Florida, 32055, United States
Clinical Trial Site
Miami, Florida, 33126, United States
Clinical Trial Site
Miami, Florida, 33135, United States
Clinical Trial Site
Miami, Florida, 33137, United States
Clinical Trial Site
Miami, Florida, 33144, United States
Clinical Trial Site
Miami, Florida, 33155, United States
Clinical Trial Site
Miami, Florida, 33176, United States
Clinical Trial Site
Miramar, Florida, 33027, United States
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Orlando, Florida, 32801, United States
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The Villages, Florida, 32162, United States
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Winter Haven, Florida, 33880, United States
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Acworth, Georgia, 30101, United States
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Atlanta, Georgia, 30322, United States
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Columbus, Georgia, 31904, United States
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Douglasville, Georgia, 30134, United States
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Gainesville, Georgia, 30501, United States
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Savannah, Georgia, 31406, United States
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Thomasville, Georgia, 31792, United States
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Boise, Idaho, 83706, United States
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Chicago, Illinois, 60602, United States
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Elkhart, Indiana, 46514, United States
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Evansville, Indiana, 47714, United States
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Richmond, Indiana, 47374, United States
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El Dorado, Kansas, 67042, United States
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Newton, Kansas, 67114, United States
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Wichita, Kansas, 67207, United States
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Owensboro, Kentucky, 42303, United States
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Monroe, Louisiana, 71201, United States
Clinical Trial Site
New Orleans, Louisiana, 70119, United States
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Boston, Massachusetts, 02114, United States
Clinical Trial Site
West Springfield, Massachusetts, 01089, United States
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Flint, Michigan, 48504, United States
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Shelby, Michigan, 48315, United States
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Ypsilanti, Michigan, 48197, United States
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Minneapolis, Minnesota, 55404, United States
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Richfield, Minnesota, 55423, United States
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Columbus, Mississippi, 39705, United States
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Tupelo, Mississippi, 38801, United States
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Creve Coeur, Missouri, 63141, United States
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Kalispell, Montana, 59901, United States
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Lincoln, Nebraska, 68510, United States
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Omaha, Nebraska, 68114, United States
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Las Vegas, Nevada, 89121, United States
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Portsmouth, New Hampshire, 03801, United States
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Berlin, New Jersey, 08009, United States
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Albuquerque, New Mexico, 87109, United States
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New York, New York, 10017, United States
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Charlotte, North Carolina, 28287, United States
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Durham, North Carolina, 27704, United States
Clinical Trial Site
Durham, North Carolina, 27713, United States
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Greensboro, North Carolina, 27401, United States
Clinical Trial Site
Greenville, North Carolina, 27834, United States
Clinical Trial Site
Monroe, North Carolina, 28112, United States
Clinical Trial Site
Raleigh, North Carolina, 27609, United States
Clinical Trial Site
Wilmington, North Carolina, 28403, United States
Clinical Trial Site
Winston-Salem, North Carolina, 27103, United States
Clinical Trial Site
Cleveland, Ohio, 44106, United States
Clinical Trial Site
Marion, Ohio, 43302, United States
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Norman, Oklahoma, 73072, United States
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Oklahoma City, Oklahoma, 73102, United States
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Bethlehem, Pennsylvania, 18017, United States
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Langhorne, Pennsylvania, 19047, United States
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Newport, Pennsylvania, 17074, United States
Clinical Trial Site
Philadelphia, Pennsylvania, 19114, United States
Clinical Trial Site
East Providence, Rhode Island, 02914, United States
Clinical Trial Site
Myrtle Beach, South Carolina, 29572, United States
Clinical Trial Site
Rapid City, South Dakota, 57701, United States
Clinical Trial Site
Chattanooga, Tennessee, 37404, United States
Clinical Trial Site
Germantown, Tennessee, 38138, United States
Clinical Trial Site
Knoxville, Tennessee, 37909, United States
Clinical Trial Site
Knoxville, Tennessee, 37923, United States
Clinical Trial Site
Memphis, Tennessee, 38119, United States
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Austin, Texas, 78744, United States
Clinical Trial Site
Coppell, Texas, 75019, United States
Clinical Trial Site
Dallas, Texas, 75230, United States
Clinical Trial Site
Dallas, Texas, 75234, United States
Clinical Trial Site
El Paso, Texas, 79925, United States
Clinical Trial Site
El Paso, Texas, 79935, United States
Clinical Trial Site
Houston, Texas, 77002, United States
Clinical Trial Site
Houston, Texas, 77024, United States
Clinical Trial Site
Houston, Texas, 77054, United States
Clinical Trial Site
Houston, Texas, 77081, United States
Clinical Trial Site
Houston, Texas, 77099, United States
Clinical Trial Site
Magnolia, Texas, 77355, United States
Clinical Trial Site
San Antonio, Texas, 78229, United States
Clinical Trial Site
San Antonio, Texas, 78240, United States
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Shenandoah, Texas, 77384, United States
Clinical Trial Site
Sherman, Texas, 75092, United States
Clinical Trial Site
Stephenville, Texas, 76401, United States
Clinical Trial Site
Tomball, Texas, 77375, United States
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Burlington, Vermont, 05401, United States
Clinical Trial Site
Burke, Virginia, 22015, United States
Clinical Trial Site
Manassas, Virginia, 20109, United States
Clinical Trial Site
Norfolk, Virginia, 23504, United States
Clinical Trial Site
West Allis, Wisconsin, 53227, United States
Clinical Trial Site
Blacktown, 2148, Australia
Clinical Trial Site
Brookvale, 2100, Australia
Clinical Trial Site
Bruce, 2617, Australia
Clinical Trial Site
Concord, 2139, Australia
Clinical Trial Site
Garran, 2605, Australia
Clinical Trial Site
Kanwal, 2259, Australia
Clinical Trial Site
Kogarah, 2217, Australia
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Perth, 6000, Australia
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Sippy Downs, 4556, Australia
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St Leonards, 2065, Australia
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Tarragindi, 4121, Australia
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Brampton, L6T 0G1, Canada
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Chicoutimi, G7H 7K9, Canada
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Greenfield Park, J4V 2G8, Canada
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Montreal, H4J 1C5, Canada
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Montreal, H4N 2W2, Canada
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Québec, G1W 4R4, Canada
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Québec, G1V 4T3, Canada
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Sainte-Foy, G1V 4G5, Canada
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Sarnia, N7T 4X3, Canada
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Toronto, M3J 0K2, Canada
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Toronto, M4P 1E4, Canada
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Toronto, M5B 1W8, Canada
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Trois-Rivières, G9A 4P3, Canada
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Waterloo, N2T 0C1, Canada
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Winnipeg, R2V 3M3, Canada
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Ponce, 00716, Puerto Rico
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Toa Baja, 00949, Puerto Rico
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Basel, 4031, Switzerland
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Geneva, 1205, Switzerland
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Lausanne, 1005, Switzerland
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Lucerne, 6000, Switzerland
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Bellshill, ML4 3NJ, United Kingdom
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Birmingham, B15 2SQ, United Kingdom
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Bristol, BS2 8HW, United Kingdom
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Canterbury, CT1 3NG, United Kingdom
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Cardiff, CF15 9SS, United Kingdom
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Carshalton, SM5 1AA, United Kingdom
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Chesterfield, S40 4AA, United Kingdom
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Chorley, PR7 7NA, United Kingdom
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Fowey, PL23 1DT, United Kingdom
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Glasgow, G20 7BE, United Kingdom
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Glasgow, G51 4TF, United Kingdom
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Hexham, NE46 1QJ, United Kingdom
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Leicester, LE5 4PW, United Kingdom
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Liskeard, PL14 3XA, United Kingdom
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Liverpool, L22 0LG, United Kingdom
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London, EC1A 7BE, United Kingdom
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London, SE1 1YR, United Kingdom
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London, SW17 0QT, United Kingdom
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Luton, LU4 0DZ, United Kingdom
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Manchester, M15 6SE, United Kingdom
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Newquay, TR7 1RU, United Kingdom
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Pickering, YO18 8BL, United Kingdom
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Plymouth, PL5 3JB, United Kingdom
Clinical Trial Site
Torpoint, PL11 2TB, United Kingdom
Related Publications (1)
Sayer M, Webb DJ, Dhaun N. Novel pharmacological approaches to lowering blood pressure and managing hypertension. Nat Rev Cardiol. 2025 Sep;22(9):649-663. doi: 10.1038/s41569-025-01131-4. Epub 2025 Feb 7.
PMID: 39920248DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 15, 2024
First Posted
February 22, 2024
Study Start
February 29, 2024
Primary Completion
June 19, 2025
Study Completion
December 1, 2025
Last Updated
March 2, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.