Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
NCT ID: NCT05103332
Last Updated: 2025-11-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
663 participants
INTERVENTIONAL
2021-11-05
2024-09-13
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Placebo (Add-on to Indapamide)
Following a 4-week run-in treatment on indapamide, 2.5 milligrams (mg), orally, once daily (QD), eligible participants were randomized to receive placebo matched to zilebesiran as a subcutaneous (SC) injection on Day 1 of 6-month double-blind (DB) treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran once every 6 months (Q6M) during the open-label extension (OLE) period. Upon implementation of Amendment 3, the OLE period was closed.
Indapamide
Indapamide administered orally
Placebo
Placebo administered by SC injection
Zilebesiran
Zilebesiran administered by SC injection
Zilebesiran (Add-on to Indapamide)
Following a 4-week run-in treatment on indapamide, 2.5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to indapamide. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Indapamide
Indapamide administered orally
Zilebesiran
Zilebesiran administered by SC injection
Placebo (Add-on to Amlodipine)
Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Amlodipine
Amlodipine administered orally
Placebo
Placebo administered by SC injection
Zilebesiran
Zilebesiran administered by SC injection
Zilebesiran (Add-on to Amlodipine)
Following a 4-week run-in treatment on amlodipine, 5 mg, orally, QD, eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to amlodipine. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Amlodipine
Amlodipine administered orally
Zilebesiran
Zilebesiran administered by SC injection
Placebo (Add-on to Olmesartan)
Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 milliliters per minute \[mL/min\] at screening enrolled at sites outside of the United States \[US\] consistent with local labeling), eligible participants were randomized to receive placebo matched to zilebesiran as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Olmesartan
Olmesartan administered orally
Placebo
Placebo administered by SC injection
Zilebesiran
Zilebesiran administered by SC injection
Zilebesiran (Add-on to Olmesartan)
Following a 4-week run-in treatment on olmesartan, 40 mg, orally, QD, (or 20 mg, orally, QD for participants with creatinine clearance ≤60 mL/min at screening enrolled at sites outside of the US consistent with local labeling), eligible participants were randomized to receive zilebesiran 600 mg, as a SC injection on Day 1 of 6-month DB treatment period as add-on therapy to olmesartan. Participants received protocol-assigned background medication for 6 months, after which it was discontinued. Thereafter, participants will receive zilebesiran, Q6M during the OLE period. Upon implementation of Amendment 3, the OLE period was closed.
Olmesartan
Olmesartan administered orally
Zilebesiran
Zilebesiran administered by SC injection
Interventions
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Indapamide
Indapamide administered orally
Amlodipine
Amlodipine administered orally
Olmesartan
Olmesartan administered orally
Placebo
Placebo administered by SC injection
Zilebesiran
Zilebesiran administered by SC injection
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. ≥155 mmHg and ≤180 mmHg for patients with untreated hypertension
2. ≥145 mmHg and ≤180 mmHg for patients on antihypertensive medications
* 24-hour mean SBP ≥130 mmHg and ≤160 mmHg by ABPM after at least 4 weeks of run-in
Exclusion Criteria
* Elevated potassium \<lower limit of normal (LLN) range or \>5 milliequivalents per liter (mEq/L)
* Estimated glomerular filtration rate (eGFR) of \<30 mL/min/1.73m\^2
* Received an investigational agent within the last 30 days
* Type 1 diabetes mellitus, poorly controlled Type 2 diabetes mellitus, or laboratory evidence of diabetes during screening without known diagnosis of diabetes
* History of any cardiovascular event within 6 months prior to randomization
* History of intolerance to SC injection(s)
18 Years
75 Years
ALL
No
Sponsors
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Alnylam Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Alnylam Pharmaceuticals
Locations
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Clinical Trial Site
Riga, , Latvia
Clinical Trial Site
Mesa, Arizona, United States
Clinical Trial Site
Tempe, Arizona, United States
Clinical Trial Site
Tempe, Arizona, United States
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Bell Gardens, California, United States
Clinical Trials Site
Beverly Hills, California, United States
Clinical Trial Site
Canoga Park, California, United States
Clinical Trial Site
Carlsbad, California, United States
Clinical Trial Site
Encinitas, California, United States
Clinical Trial Site
Garden Grove, California, United States
Clinical Trial Site
Hollywood, California, United States
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Huntington Beach, California, United States
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Irvine, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Mission Hills, California, United States
Clinical Trial Site
Oceanside, California, United States
Clinical Trial Site
Panorama City, California, United States
Clinical Trial Site
San Diego, California, United States
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Santa Clarita, California, United States
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South Gate, California, United States
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Tustin, California, United States
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Upland, California, United States
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Washington D.C., District of Columbia, United States
Clinical Trial Site
Clearwater, Florida, United States
Clinical Trial Site
Coconut Creek, Florida, United States
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Coral Gables, Florida, United States
Clinical Trial Site
Hollywood, Florida, United States
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Hollywood, Florida, United States
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Inverness, Florida, United States
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Jacksonville, Florida, United States
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Miami, Florida, United States
Clinical Trial Site
Miami, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Naples, Florida, United States
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Orlando, Florida, United States
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Orlando, Florida, United States
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Pembroke Pines, Florida, United States
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Tampa, Florida, United States
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Winter Haven, Florida, United States
Clinical Trial Site
Winter Park, Florida, United States
Clinical Trial Site
Acworth, Georgia, United States
Clinical Trial Site
Canton, Georgia, United States
Clinical Trial Site
Columbus, Georgia, United States
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Savannah, Georgia, United States
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Louisville, Kentucky, United States
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New Orleans, Louisiana, United States
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Southgate, Michigan, United States
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Jackson, Mississippi, United States
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Hazelwood, Missouri, United States
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Jefferson City, Missouri, United States
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New York, New York, United States
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Greensboro, North Carolina, United States
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Greensboro, North Carolina, United States
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Monroe, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Norman, Oklahoma, United States
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Little River, South Carolina, United States
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Memphis, Tennessee, United States
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Amarillo, Texas, United States
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Coppell, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Houston, Texas, United States
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Lake Jackson, Texas, United States
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Plano, Texas, United States
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Sherman, Texas, United States
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Splendora, Texas, United States
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Stephenville, Texas, United States
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Tomball, Texas, United States
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Waco, Texas, United States
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Burke, Virginia, United States
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Kenosha, Wisconsin, United States
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Brampton, Ontario, Canada
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Concord, Ontario, Canada
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Winnipeg, Ontario, Canada
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Chicoutimi, Quebec, Canada
Clinical Trial Site
Lévis, Quebec, Canada
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Pointe-Claire, Quebec, Canada
Clinical Trial Site
Québec, Quebec, Canada
Clinical Trial Site
Sherbrooke, Quebec, Canada
Clinical Trial Site
Trois-Rivières, Quebec, Canada
Clinical Trial Site
Québec, , Canada
Clinical Trial Site
Tartu, , Estonia
Clinical Trial Site
Frankfurt, , Germany
Clinical Trial Site
Kaunas, , Lithuania
Clinical Trial Site
Vilnius, , Lithuania
Clinical Trial Site
Częstochowa, , Poland
Clinical Trial Site
Gdansk, , Poland
Clinical Trial Site
Katowice, , Poland
Clinical Trial Site
Staszów, , Poland
Clinical Trial Site
Warsaw, , Poland
Clinical Trial Site
Wroclaw, , Poland
Clinical Trial Site
Bellshill, Lanarkshire, United Kingdom
Clinical Trial Site
Carshalton, , United Kingdom
Clinical Trial Site
Edinburgh, , United Kingdom
Clinical Trial Site
Fowey, , United Kingdom
Clinical Trial Site
Glasgow, , United Kingdom
Clinical Trial Site
Lancashire Preston, , United Kingdom
Clinical Trial Site
Liskeard, , United Kingdom
Clinical Trial Site
London, , United Kingdom
Clinical Trial Site
Manchester, , United Kingdom
Clinical Trial Site
Newquay, , United Kingdom
Clinical Trial Site
Plymouth, , United Kingdom
Clinical Trial Site
Sheffield, , United Kingdom
Clinical Trial Site
Torpoint, , United Kingdom
Countries
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References
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Desai AS, Karns AD, Badariene J, Aswad A, Neutel JM, Kazi F, Park W, Stiglitz D, Makarova N, Havasi A, Zappe DH, Saxena M; KARDIA-2 Study Group. Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial. JAMA. 2025 Jul 1;334(1):46-55. doi: 10.1001/jama.2025.6681.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2021-003776-13
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ALN-AGT01-003
Identifier Type: -
Identifier Source: org_study_id
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