Trial results for the KARDIA-2 study (NCT05103332) investigating zilebesiran as add-on therapy for hypertension were posted on ClinicalTrials.gov on 2025-07-09. The study demonstrated that zilebesiran significantly reduced 24-hour mean systolic blood pressure (SBP) compared to placebo when added to standard antihypertensive medications. For patients on indapamide, zilebesiran showed a difference of -12.1 mmHg in SBP reduction compared to placebo.

Background

The KARDIA-2 study, formally titled "Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication," aimed to evaluate the effect of zilebesiran on systolic and diastolic blood pressure and to characterize its pharmacodynamic effects and safety as add-on therapy for hypertension.

Trial design

The KARDIA-2 study (NCT05103332) was a Phase 2, completed trial that enrolled 663 participants with hypertension not adequately controlled by a standard of care antihypertensive medication. The study investigated zilebesiran as an add-on therapy. Participants received zilebesiran or placebo in combination with either indapamide, amlodipine, or olmesartan. The study's primary objective was to evaluate the effect of zilebesiran on systolic and diastolic blood pressure.

Key results

The KARDIA-2 trial demonstrated statistically significant reductions in systolic blood pressure when zilebesiran was added to standard antihypertensive medications. Key findings for the difference in least squares mean (LS Mean) change from baseline in 24-hour mean SBP assessed by ABPM at Month 3 (censored data) include:

For office SBP at Month 3 (censored data) when added to indapamide, the difference in LS Mean was -18.5 mmHg (95.0% CI: -22.8 to -14.2) with a p-value of 0.0001. The zilebesiran group's change was -19.3 mmHg (Standard Error: 1.52) vs. -0.8 mmHg (Standard Error: 1.55) for placebo.

Time-adjusted changes from baseline through Month 6 in 24-hour mean SBP (all collected data) when added to indapamide showed a difference in LS Mean of -11.0 mmHg (95.0% CI: -14.7 to -7.3) with a p-value of 0.0001. The zilebesiran group's change was -15.6 mmHg (Standard Error: 1.35) vs. -4.6 mmHg (Standard Error: 1.30) for placebo.

Time-adjusted changes from baseline through Month 6 in office SBP (all collected data) when added to indapamide showed a difference in LS Mean of -13.6 mmHg (95.0% CI: -16.9 to -10.3) with a p-value of 0.0001. The zilebesiran group's change was -18.1 mmHg (Standard Error: 1.18) vs. -4.5 mmHg (Standard Error: 1.16) for placebo.

What this means

The results from the KARDIA-2 trial indicate that zilebesiran, when used as an add-on therapy, significantly lowers both 24-hour mean and office systolic blood pressure in patients with hypertension not adequately controlled by existing medications. The consistent and statistically significant reductions observed across different background antihypertensive regimens (indapamide, amlodipine, olmesartan) suggest that zilebesiran could be a valuable new treatment option for managing resistant hypertension. These findings provide important data for clinicians considering strategies to achieve better blood pressure control in their patients.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05103332, titled "Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)," were posted on 2025-07-09 on clinicaltrials.gov.