Trial · NCT05103332
Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
NCT05103332, Phase 2, Completed, Alnylam Pharmaceuticals; results first posted 2025-07-09
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2). Trials, record NCT05103332. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT05103332
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)
- NCT number
- NCT05103332
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 663 participants, actual
- Lead sponsor
- Alnylam Pharmaceuticals
- Conditions
- Hypertension
- Interventions
- Indapamide, Amlodipine, Olmesartan, Placebo, Zilebesiran
- First posted
- 2021-11-02
- Last updated
- 2025-11-03
- Other registries' IDs
- eudract:2021-003776-13
- Results first posted
- 2025-07-09
Source ClinicalTrials.gov
Registered outcomes45
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | Baseline and Month 3 | 24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. Least squares (LS) mean and standard error (SE) were calculated using a mixed model repeated measures (MMRM) approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint. |
| Primary | Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | Baseline and Month 3 | 24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was the average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint. |
| Primary | Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | Baseline and Month 3 | 24-hour ABPM device was programmed to take readings every 20 minutes during day (6 am- 9:59 pm) and every 30 minutes during night (10 pm-5:59 am). ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e.,3 sections of 60 minutes where 0 valid readings were obtained). To summarize 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint. |
| Secondary | Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data | Baseline and Month 3 | The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office SBP assessed while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint. |
| Secondary | Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data | Baseline through Month 6 | Time-adjusted change was defined as the area under the curve (AUC) of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for SBP assessed by ABPM, were included in the analysis for this endpoint. |
| Secondary | Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data | Baseline through Month 6 | Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Treatment policy strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., all collected data for office SBP were included in the analysis for this endpoint. |
| Secondary | Indapamide: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6 | Month 6 | 24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average of BP for each hour of the day. The 24-hour mean was average of the hourly means. |
| Secondary | Indapamide: Change From Baseline at Month 3 in 24-hour Mean Diastolic Blood Pressure (DBP), Assessed by ABPM - Censored Data | Baseline and Month 3 | 24-hour ABPM device was programmed to take readings every 20 minutes during the day (6 am to 9:59 pm) and every 30 minutes during the night (10 pm to 5:59 am). An ABPM was considered adequate if: 1. the number of successful daytime readings were ≥33; 2. the number of successful nighttime readings were ≥11; 3. no more than 3 hours are not represented (i.e., 3 sections of 60 minutes where 0 valid readings were obtained). To summarize the 24-hour ABPM, the hourly adjusted mean was calculated. Hourly adjusted mean was the average BP for each hour of the day. The 24-hour mean was average of the hourly means. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for DBP assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint. |
| Secondary | Indapamide: Change From Baseline at Month 3 in Office DBP - Censored Data | Baseline and Month 3 | The mean office BP in the sitting position was used for the analysis. Office BP in the sitting position was collected with a set of 4 replicates. The average of the last 3 replicates was calculated and used for analysis. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for office DBP assessed while participants were on and within 2 weeks after stopping any escape medication was censored for this endpoint. |
| Secondary | Indapamide: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data | Baseline through Month 3 | Time-adjusted change was defined as the AUC of BP change from baseline divided by the duration of the time period. LS mean and SE were calculated using a MMRM approach. Hypothetical strategy was used for the intercurrent event of using antihypertensive escape medication, i.e., data for SBP and DBP, assessed using ABPM, while participants were on and within 2 weeks after stopping any escape medication were censored for this endpoint. |
1 to 10 of 45Source ClinicalTrials.gov
See all 45 registered outcomesOutcomes45
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | Baseline and Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
| PRIMARY | Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | Baseline and Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
| PRIMARY | Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | Baseline and Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm.~Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data | Baseline and Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data | Baseline through Month 6 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Indapamide: Time-adjusted Change From Baseline Through Month 6 in Office SBP - All Collected Data | Baseline through Month 6 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Indapamide: Percentage of Participants With 24-hour Mean SBP <130 mmHg and/or Reduction From Baseline ≥20 mmHg Assessed by ABPM Without Escape Antihypertensive Medications at Month 6 | Month 6 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 6. | percentage of participants | NUMBER |
| SECONDARY | Indapamide: Change From Baseline at Month 3 in 24-hour Mean Diastolic Blood Pressure (DBP), Assessed by ABPM - Censored Data | Baseline and Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Indapamide: Change From Baseline at Month 3 in Office DBP - Censored Data | Baseline and Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
| SECONDARY | Indapamide: Time-adjusted Change From Baseline Through Month 3 in 24-hour Mean SBP and DBP, Assessed by ABPM - Censored Data | Baseline through Month 3 | The mFAS included all randomized participants who received any amount of study drug. Analysis was grouped according to the randomized treatment arm. Overall number analyzed is the number of participants with data available for analysis at Month 3. | mmHg | LEAST_SQUARES_MEAN |
1 to 10 of 45Source ClinicalTrials.gov
See all 45 outcomesResults by group216
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | DB Period: Placebo (Add-on to Indapamide) | -3.7 | Standard Error 1.56 | mmHg | |
| Indapamide: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | DB Period: Zilebesiran (Add-on to Indapamide) | -15.7 | Standard Error 1.60 | mmHg | |
| Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | DB Period: Placebo (Add-on to Amlodipine) | -0.7 | Standard Error 1.14 | mmHg | |
| Amlodipine: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | DB Period: Zilebesiran (Add-on to Amlodipine) | -10.5 | Standard Error 1.15 | mmHg | |
| Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | DB Period: Placebo (Add-on to Olmesartan) | -3.2 | Standard Error 1.34 | mmHg | |
| Olmesartan: Change From Baseline at Month 3 in 24-hour Mean SBP Assessed by ABPM - Censored Data | DB Period: Zilebesiran (Add-on to Olmesartan) | -7.7 | Standard Error 1.33 | mmHg | |
| Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data | DB Period: Placebo (Add-on to Indapamide) | -0.8 | Standard Error 1.55 | mmHg | |
| Indapamide: Change From Baseline at Month 3 in Office SBP - Censored Data | DB Period: Zilebesiran (Add-on to Indapamide) | -19.3 | Standard Error 1.52 | mmHg | |
| Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data | DB Period: Placebo (Add-on to Indapamide) | -4.6 | Standard Error 1.30 | mmHg | |
| Indapamide: Time-adjusted Change From Baseline Through Month 6 in 24-hour Mean SBP, Assessed by ABPM - All Collected Data | DB Period: Zilebesiran (Add-on to Indapamide) | -15.6 | Standard Error 1.35 | mmHg |
1 to 10 of 216Source ClinicalTrials.gov
See all 216 results by groupParticipant flow198
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| DB Period (6 Months=168 Days) | STARTED | DB Period: Placebo (Add-on to Indapamide) | 65 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period: Zilebesiran (Add-on to Indapamide) | 65 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period: Placebo (Add-on to Amlodipine) | 120 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period: Zilebesiran (Add-on to Amlodipine) | 120 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period: Placebo (Add-on to Olmesartan) | 146 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period: Zilebesiran (Add-on to Olmesartan) | 147 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period (Placebo) to OLE Period (Zilebesiran) [Indapamide Cohort] | 0 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Indapamide Cohort] | 0 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period (Placebo) to OLE Period (Zilebesiran) [Amlodipine Cohort] | 0 | |
| DB Period (6 Months=168 Days) | STARTED | DB Period (Zilebesiran) to OLE Period (Zilebesiran) [Amlodipine Cohort] | 0 |
1 to 10 of 198Source ClinicalTrials.gov
See all 198 participant flowAdverse events924
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Injection site reaction | General disorders | Run-in: Indapamide | 0 | 127 | |
| other | Injection site reaction | General disorders | Run-in: Amlodipine | 0 | 238 | |
| other | Injection site reaction | General disorders | Run-in: Olmesartan | 0 | 293 | |
| other | Injection site reaction | General disorders | DB Period: Placebo (Add-on to Indapamide) | 0 | 64 | |
| other | Injection site reaction | General disorders | DB Period: Zilebesiran (Add-on to Indapamide) | 4 | 63 | |
| other | Injection site reaction | General disorders | DB Period: Placebo (Add-on to Amlodipine) | 0 | 120 | |
| other | Injection site reaction | General disorders | DB Period: Zilebesiran (Add-on to Amlodipine) | 2 | 118 | |
| other | Injection site reaction | General disorders | DB Period: Placebo (Add-on to Olmesartan) | 1 | 145 | |
| other | Injection site reaction | General disorders | DB Period: Zilebesiran (Add-on to Olmesartan) | 4 | 148 | |
| other | Injection site reaction | General disorders | DB Period (Placebo) to OLE Period (Zilebesiran) [Indapamide Cohort] | 0 | 26 |
1 to 10 of 924Source ClinicalTrials.gov
See all 924 adverse eventsAdverse event totals63
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Run-in: Indapamide | 0 | 127 |
| Total, all-cause mortality | Run-in: Amlodipine | 0 | 238 |
| Total, all-cause mortality | Run-in: Olmesartan | 0 | 293 |
| Total, all-cause mortality | DB Period: Placebo (Add-on to Indapamide) | 0 | 64 |
| Total, all-cause mortality | DB Period: Zilebesiran (Add-on to Indapamide) | 0 | 63 |
| Total, all-cause mortality | DB Period: Placebo (Add-on to Amlodipine) | 0 | 120 |
| Total, all-cause mortality | DB Period: Zilebesiran (Add-on to Amlodipine) | 0 | 118 |
| Total, all-cause mortality | DB Period: Placebo (Add-on to Olmesartan) | 0 | 145 |
| Total, all-cause mortality | DB Period: Zilebesiran (Add-on to Olmesartan) | 0 | 148 |
| Total, all-cause mortality | DB Period (Placebo) to OLE Period (Zilebesiran) [Indapamide Cohort] | 0 | 26 |
1 to 10 of 63Source ClinicalTrials.gov
See all 63 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 40434761 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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Read this trial from software.
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GET https://conductscience.org/api/trials/v1/NCT05103332/registered?page=2