Zilebesiran as Add-on Therapy in Patients With High Cardiovascular Risk and Hypertension Not Adequately Controlled by Standard of Care Antihypertensive Medications (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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06272487

Acronym

KARDIA-3

Enrollment

375

Registered

2024-02-22

Start date

2024-02-29

Completion date

2025-12-01

Last updated

2026-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

High Cardiovascular Risk, Hypertension

Keywords

High blood pressure, Hypertension, siRNA, Angiotensinogen, AGT, Cardiovascular disease, Chronic kidney disease, Uncontrolled hypertension

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.

Interventions

DRUGZilebesiran

Zilebesiran administered by subcutaneous (SC) injection

DRUGPlacebo

Placebo administered by SC injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame
Change from Baseline at Month 3 in Mean Seated Office Systolic Blood Pressure (SBP)	Baseline and Month 3

Secondary

Measure	Time frame
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
Change from Baseline at Month 3 and Month 6 in Daytime and Nighttime Mean SBP and Diastolic Blood Pressure (DBP) assessed by ABPM	Baseline and Months 3 and 6
Change from Baseline at Month 3 and Month 6 in Mean Seated Office DBP	Baseline and Months 3 and 6
Change from Baseline at Month 3 and Month 6 in 24-hour Mean DBP Assessed by ABPM	Baseline and Months 3 and 6
Change from Baseline Over Time in Serum Angiotensinogen (AGT)	Baseline through Month 6

Countries

Australia, Canada, Puerto Rico, Switzerland, United Kingdom, United States

Contacts

STUDY_DIRECTORMedical Director

Alnylam Pharmaceuticals

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 3, 2026