Clinical trial NCT06272487: Zilebesiran as Add-on Therapy in Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications (KARDIA-3)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: High Cardiovascular Risk
Hypertension
Keywords: High blood pressure
Hypertension
siRNA
Angiotensinogen
AGT
Cardiovascular disease
Chronic kidney disease
Uncontrolled hypertension
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-02-22
Enrollment: 375
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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
* 24-hour mean SBP ≥130 mmHg and ≤170 mmHg assessed by ABPM
* Must be on stable therapy with 2 to 4 classes of antihypertensive medications

Exclusion Criteria:

* Secondary hypertension
* Orthostatic hypotension
* Proteinuria \>3 g/day
* Serum potassium \>4.8 milliequivalents per liter (mEq/L)

Primary outcomes:
measure: Change from Baseline at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP)
timeFrame: Baseline and Month 3
Secondary outcomes:
measure: Change from Baseline at Month 3 in 24-Hour Mean SBP Assessed by Ambulatory Blood Pressure Monitoring (ABPM)
timeFrame: Baseline and Month 3
measure: Change from Baseline at Month 6 in Mean Seated Office SBP
timeFrame: Baseline and Month 6
measure: Change from Baseline at Month 6 in 24-Hour Mean SBP Assessed by ABPM
timeFrame: Baseline and Month 6
measure: Proportion of Patients with Mean Seated Office SBP <140 mmHg and/or Reduction ≥10 mmHg without Intensification of Antihypertensive Regimen at Month 6
timeFrame: Month 6
measure: 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
timeFrame: Month 6
measure: Change from Baseline at Month 3 and Month 6 in Daytime and Nighttime Mean SBP and Diastolic Blood Pressure (DBP) assessed by ABPM
timeFrame: Baseline and Months 3 and 6
measure: Change from Baseline at Month 3 and Month 6 in Mean Seated Office DBP
timeFrame: Baseline and Months 3 and 6
measure: Change from Baseline at Month 3 and Month 6 in 24-hour Mean DBP Assessed by ABPM
timeFrame: Baseline and Months 3 and 6
measure: Change from Baseline Over Time in Serum Angiotensinogen (AGT)
timeFrame: Baseline through Month 6
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Clinical Trial Site
state: Alabama
city: Daphne
country: United States
facility: Clinical Trial Site
state: Alabama
city: Foley
country: United States
facility: Clinical Trial Site
state: Alabama
city: Huntsville
country: United States
facility: Clinical Trial Site
state: Alabama
city: Huntsville
country: United States
facility: Clinical Trial Site
state: Alabama
city: Montgomery
country: United States
facility: Clinical Trial Site
state: Alabama
city: Gilbert
country: United States
facility: Clinical Trial Site
state: Arizona
city: Phoenix
country: United States
facility: Clinical Trial Site
state: Arizona
city: Sun City
country: United States
facility: Clinical Trial Site
state: Arizona
city: Tempe
country: United States
facility: Clinical Trial Site
state: Arizona
city: Tucson
country: United States
facility: Clinical Trial Site
state: Arizona
city: Beverly Hills
country: United States
facility: Clinical Trial Site
state: California
city: Covina
country: United States
facility: Clinical Trial Site
state: California
city: Encinitas
country: United States
facility: Clinical Trial Site
state: California
city: Garden Grove
country: United States
facility: Clinical Trial Site
state: California
city: Huntington Beach
country: United States
facility: Clinical Trial Site
state: California
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Northridge
country: United States
facility: Clinical Trial Site
state: California
city: Northridge
country: United States
facility: Clinical Trial Site
state: California
city: Pasadena
country: United States
facility: Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: San Dimas
country: United States
facility: Clinical Trial Site
state: California
city: Santa Ana
country: United States
facility: Clinical Trial Site
state: California
city: Simi Valley
country: United States
facility: Clinical Trial Site
state: California
city: Vacaville
country: United States
facility: Clinical Trial Site
state: California
city: Van Nuys
country: United States
facility: Clinical Trial Site
state: California
city: West Hills
country: United States
facility: Clinical Trial Site
state: California
city: Colorado Springs
country: United States
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state: Colorado
city: Denver
country: United States
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state: Colorado
city: Denver
country: United States
facility: Clinical Trial Site
state: Colorado
city: Hartford
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Middlebury
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Waterbury
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Washington
country: United States
facility: Clinical Trial Site
state: District of Columbia
city: Clearwater
country: United States
facility: Clinical Trial Site
state: Florida
city: Coral Gables
country: United States
facility: Clinical Trial Site
state: Florida
city: Daytona Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Fort Myers
country: United States
facility: Clinical Trial Site
state: Florida
city: Hollywood
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Jensen Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Lake City
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: North Miami Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: Pembroke Pines
country: United States
facility: Clinical Trial Site
state: Florida
city: The Villages
country: United States
facility: Clinical Trial Site
state: Florida
city: Winter Haven
country: United States
facility: Clinical Trial Site
state: Florida
city: Acworth
country: United States
facility: Clinical Trial Site
state: Georgia
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: Douglasville
country: United States
facility: Clinical Trial Site
state: Georgia
city: Gainesville
country: United States
facility: Clinical Trial Site
state: Georgia
city: Savannah
country: United States
facility: Clinical Trial Site
state: Georgia
city: Thomasville
country: United States
facility: Clinical Trial Site
state: Georgia
city: Boise
country: United States
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state: Idaho
city: Chicago
country: United States
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state: Illinois
city: Elkhart
country: United States
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state: Indiana
city: Evansville
country: United States
facility: Clinical Trial Site
state: Indiana
city: Richmond
country: United States
facility: Clinical Trial Site
state: Indiana
city: El Dorado
country: United States
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state: Kansas
city: Newton
country: United States
facility: Clinical Trial Site
state: Kansas
city: Wichita
country: United States
facility: Clinical Trial Site
state: Kansas
city: Owensboro
country: United States
facility: Clinical Trial Site
state: Kentucky
city: Monroe
country: United States
facility: Clinical Trial Site
state: Louisiana
city: New Orleans
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Springfield
country: United States
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state: Massachusetts
city: Flint
country: United States
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state: Michigan
city: Roseville
country: United States
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state: Michigan
city: Ypsilanti
country: United States
facility: Clinical Trial Site
state: Michigan
city: Edina
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Minneapolis
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Columbus
country: United States
facility: Clinical Trial Site
state: Mississippi
city: Tupelo
country: United States
facility: Clinical Trial Site
state: Mississippi
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: Kalispell
country: United States
facility: Clinical Trial Site
state: Montana
city: Lincoln
country: United States
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state: Nebraska
city: Omaha
country: United States
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state: Nebraska
city: Las Vegas
country: United States
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state: Nevada
city: Portsmouth
country: United States
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state: New Hampshire
city: Berlin
country: United States
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state: New Jersey
city: Albuquerque
country: United States
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state: New Mexico
city: New York
country: United States
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state: New York
city: Charlotte
country: United States
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state: North Carolina
city: Durham
country: United States
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state: North Carolina
city: Durham
country: United States
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state: North Carolina
city: Greensboro
country: United States
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state: North Carolina
city: Greenville
country: United States
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state: North Carolina
city: Monroe
country: United States
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state: North Carolina
city: Raleigh
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Wilmington
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Marion
country: United States
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state: Ohio
city: Norman
country: United States
facility: Clinical Trial Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Clinical Trial Site
state: Oklahoma
city: Bethlehem
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Camp Hill
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Langhorne
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Philadelphia
country: United States
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state: Pennsylvania
city: East Providence
country: United States
facility: Clinical Trial Site
state: Rhode Island
city: Myrtle Beach
country: United States
facility: Clinical Trial Site
state: South Carolina
city: Rapid City
country: United States
facility: Clinical Trial Site
state: South Dakota
city: Chattanooga
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Germantown
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Knoxville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Knoxville
country: United States
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state: Tennessee
city: Memphis
country: United States
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state: Tennessee
city: Austin
country: United States
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state: Texas
city: Coppell
country: United States
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state: Texas
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Dallas
country: United States
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state: Texas
city: El Paso
country: United States
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state: Texas
city: El Paso
country: United States
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state: Texas
city: El Paso
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
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state: Texas
city: Shenandoah
country: United States
facility: Clinical Trial Site
state: Texas
city: Sherman
country: United States
facility: Clinical Trial Site
state: Texas
city: Splendora
country: United States
facility: Clinical Trial Site
state: Texas
city: Stephenville
country: United States
facility: Clinical Trial Site
state: Texas
city: Tomball
country: United States
facility: Clinical Trial Site 1 - Tomball
state: Texas
city: Tomball
country: United States
facility: Clinical Trial Site 2 - Tomball
state: Texas
city: Burlington
country: United States
facility: Clinical Trial Site
state: Vermont
city: Burke
country: United States
facility: Clinical Trial Site
state: Virginia
city: Manassas
country: United States
facility: Clinical Trial Site
state: Virginia
city: Norfolk
country: United States
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state: Virginia
city: Wauwatosa
country: United States
facility: Clinical Trial Site
state: Wisconsin
city: Bruce
country: Australia
facility: Clinical Trial Site
state: Australian Capital Territory
city: Sydney
country: Australia
facility: Clinical Trial Site
state: Australian Capital Territory
city: Brookvale
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Concord
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Kanwal
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Kogarah
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Sherwood
country: Australia
facility: Clinical Trial Site
state: Queensland
city: Sippy Downs
country: Australia
facility: Clinical Trial Site
state: Queensland
city: Garran
country: Australia
facility: Clinical Trial Site
city: Perth
country: Australia
facility: Clinical Trial Site
city: Winnipeg
country: Canada
facility: Clinical Trial Site
state: Manitoba
city: Sarnia
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Waterloo
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Greenfield Park
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Montreal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Montréal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Québec
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Quebec
country: Canada
facility: Clinical Trial Site
city: Bayamon
country: Puerto Rico
facility: Clinical Trial Site
city: Ponce
country: Puerto Rico
facility: Clinical Trial Site
city: Basel
country: Switzerland
facility: Clinical Trial Site
city: Geneva
country: Switzerland
facility: Clinical Trial Site
city: Lausanne
country: Switzerland
facility: Clinical Trial Site
city: Luzern
country: Switzerland
facility: Clinical Trial Site
city: Luton
country: United Kingdom
facility: Clinical Trial Site
state: Bedfordshire
city: Luton
country: United Kingdom
facility: Clinical Trial Site
state: Bedfordshire
city: Fowey
country: United Kingdom
facility: Clinical Trial Site
state: Cornwall
city: Liskeard
country: United Kingdom
facility: Clinical Trial Site
state: Cornwall
city: Newquay
country: United Kingdom
facility: Clinical Trial Site
state: Cornwall
city: Torpoint
country: United Kingdom
facility: Clinical Trial Site
state: Cornwall
city: Chesterfield
country: United Kingdom
facility: Clinical Trial Site
state: Derbyshire
city: Plymouth
country: United Kingdom
facility: Clinical Trial Site
state: Devon
city: Bristol
country: United Kingdom
facility: Clinical Trial Site
state: Gloucestershire
city: Canterbury
country: United Kingdom
facility: Clinical Trial Site
state: Kent
city: Bellshill
country: United Kingdom
facility: Clinical Trial Site
state: Lanarkshire
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
state: Lanarkshire
city: Manchester
country: United Kingdom
facility: Clinical Trial Site
state: Lancashire
city: Leicester
country: United Kingdom
facility: Clinical Trial Site
state: Leicestershire
city: Hexham
country: United Kingdom
facility: Clinical Trial Site
state: Northumberland
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
state: Scotland
city: Carshalton
country: United Kingdom
facility: Clinical Trial Site
state: Surrey
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
city: Cardriff
country: United Kingdom
facility: Clinical Trial Site
city: Chorley
country: United Kingdom
facility: Clinical Trial Site
city: Liverpool
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Pickering
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: