Resistant HypertensionPhase 2HEVANCT04637152
Sacubitril/Valsartan in Resistant Hypertension
A Phase 2 study testing Sacubitril-Valsartan in people with Resistant Hypertension and Blood Pressure, run by Hospital Geral Roberto Santos at 2 sites in Brazil.
Trial summary
The present study aims to evaluate the antihypertensive effect of sacubitril/valsartan in patients with resistant hypertension compared to the use of recommended and optimized antihypertensive therapy, through a randomized clinical trial, over 12 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Resistant Hypertension, Blood Pressure
- What is being tested?
- Sacubitril-Valsartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesBrazil
- Study dates
- 11 Nov 2020to 17 Aug 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women, over 18;
- Diagnosed with resistant hypertension (using three or more antihypertensive agents of different classes - eg. angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blockers, loop and thiazide diuretics or potassium-sparing diuretics), at least 4 weeks before recruitment, with a BP that remains above the goal of 140/90 mmHg.
Who cannot join
- Secondary and treatable hypertension;
- History of angioedema; significant cerebrovascular disease;
- Active liver disease (alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of the normal range and)
- Kidney dialysis or kidney transplantation or serum creatinine> 1.5 times the upper limit of the normal range or CrCl <30 mL/min;
- Previous or current diagnosis of heart failure;
- Malignancy;
- Any significant laboratory abnormalities such as serum potassium > 5.5 mmol/L.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
General Hospital Roberto Santos
Salvador, Estado de Bahia, 40301-110
Hospital Universitário Professor Edgard Santos
Salvador, Estado de Bahia, 40301-155
About this study
Official title: Anti-Hypertensive Effect of Sacubitril/Valsartan in Resistant Hypertension: Randomized Clinical Trial - The HEVA Study
The present study aims to evaluate the antihypertensive effect of sacubitril/valsartan in patients with resistant hypertension compared to the use of recommended and optimized antihypertensive therapy, through a randomized clinical trial, over 12 weeks.
Read the detailed description
Worldwide, millions of people are affected by the arterial hypertension system (SAH), so that the presence of resistant hypertension (RH) significantly influences a high cardiovascular morbidity and mortality compared to those with controlled SAH, thus corroborating the need for the development of agents antihypertensive drugs with favorable efficacy and safety profiles. It is known that they are currently using the combined therapy recommended for this group of patients, among them, a significant portion of individuals with RH are unable to achieve the goal of BP control (>140/90 mmHg) even though in regular use, being subject to the greatest risk of cardiovascular outcomes and morbidity and mortality. Approved by the FDA for use in heart failure with reduced ejection fraction with beneficial effects on morbidity and mortality, identified in previous studies, the sacubitril/valsartan molecule (LCZ696) or Entresto® is a molecular complex composed of the sacubitril prodrug activated after ingestion in sacubitrilate - neprilysin inhibitor - associated with valsartan, an angiotensin II type-1 (AT1) receptor antagonist, with vasodilating action, capable of reducing BP, sympathetic tone, with antifibrotic and anti-hypertrophic effects, in addition to natriuresis and diuresis. Considering the knowledge gap to the benefits to LCZ696 in the control of blood pressure in resistant hypertension, the objective of the present study is to evaluate the efficacy (reduction of ambulatory systolic and diastolic blood pressure) and safety (adverse events, hospitalization and cardiovascular death) of the use of sacubitril/valsartan in comparison to the antihypertensive therapy recommended and optimized by the current guidelines, in patients diagnosed with RH, over12 weeks, through a randomized clinical trial.
- Conditions
- Resistant Hypertension, Blood Pressure
- Being tested
- Sacubitril-Valsartan
- Keywords
- Resistant Hypertension, LCZ696, Blood pressure control, sacubitril/valsartan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-ValsartanDrug
Use of sacubitril/valsartan after suspension of ACE inhibitors or ARBs.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Usual recommended therapy | No intervention | Antihypertensive regimen based on the usual recommended (optimized) therapy. |
| Group B: Sacubitril/Valsartan | Experimental | Suspension of ACE inhibitors - for at least 36h of the last dose - or ARB. Initial dosage: Sacubitril/valsartan 49mg/51mg, 1 tablet twice daily. Target dose (after two weeks): 97mg/103 mg, 1 tablet twice daily. Receives: Drug: Sacubitril-Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
achieving the blood pressure target of <140/90mmg and the reducing of the mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), and mean sitting pulse pressure (msPP) over an 8-week period.
2 co-primary outcomes
Measured: 8 weeks
Secondary efficacy outcomes included BP reduction stratified by Sac-Val dose compared to standard therapy.
Secondary outcome
Measured: 8 weeks
Secondary outcomes (1)
Secondary safety outcomes included incidence of acute myocardial infarction, hospitalization, stroke, hypotension, angioedema, electrolyte disturbances, CKD progression, and CV mortality
Safety outcomes
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2020
- Study start11 Nov 2020
- Primary completion22 Jul 2022
- Study completion17 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Resistant HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Geral Roberto Santos
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitário Professor Edgard Santos
- Responsible party
- Principal investigator, Andre Rodrigues Duraes, Hospital Geral Roberto Santos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04637152
- Sponsor's protocol ID
- HGeralRobertoSantos
- Acronym
- HEVA
- Status last verified
- Feb 2025
- First submitted
- 14 Nov 2020
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-Hypertensive Effect of Sacubitril/Valsartan in Resistant Hypertension: Randomized Clinical Trial - The HEVA Study
- ClinicalTrials.gov ID
- NCT04637152
- Acronym / sponsor ID
- HEVA / HGeralRobertoSantos
- Conditions
- Resistant Hypertension, Blood Pressure
- Keywords
- Resistant Hypertension, LCZ696, Blood pressure control, sacubitril/valsartan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Hospital Geral Roberto SantosUniversity, hospital or other
- Collaborators
- Hospital Universitário Professor Edgard Santos
- Study start
- 11 Nov 2020 (actual)
- Primary completion
- 22 Jul 2022 (actual)
- Study completion
- 17 Aug 2022 (actual)
- First posted
- 19 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study aims to evaluate the antihypertensive effect of sacubitril/valsartan in patients with resistant hypertension compared to the use of recommended and optimized antihypertensive therapy, through a randomized clinical trial, over 12 weeks.
Detailed description
Worldwide, millions of people are affected by the arterial hypertension system (SAH), so that the presence of resistant hypertension (RH) significantly influences a high cardiovascular morbidity and mortality compared to those with controlled SAH, thus corroborating the need for the development of agents antihypertensive drugs with favorable efficacy and safety profiles. It is known that they are currently using the combined therapy recommended for this group of patients, among them, a significant portion of individuals with RH are unable to achieve the goal of BP control (>140/90 mmHg) even though in regular use, being subject to the greatest risk of cardiovascular outcomes and morbidity and mortality. Approved by the FDA for use in heart failure with reduced ejection fraction with beneficial effects on morbidity and mortality, identified in previous studies, the sacubitril/valsartan molecule (LCZ696) or Entresto® is a molecular complex composed of the sacubitril prodrug activated after ingestion in sacubitrilate - neprilysin inhibitor - associated with valsartan, an angiotensin II type-1 (AT1) receptor antagonist, with vasodilating action, capable of reducing BP, sympathetic tone, with antifibrotic and anti-hypertrophic effects, in addition to natriuresis and diuresis. Considering the knowledge gap to the benefits to LCZ696 in the control of blood pressure in resistant hypertension, the objective of the present study is to evaluate the efficacy (reduction of ambulatory systolic and diastolic blood pressure) and safety (adverse events, hospitalization and cardiovascular death) of the use of sacubitril/valsartan in comparison to the antihypertensive therapy recommended and optimized by the current guidelines, in patients diagnosed with RH, over12 weeks, through a randomized clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)
| Arm | Type | Receives |
|---|---|---|
| Group A: Usual recommended therapy | No intervention | –Antihypertensive regimen based on the usual recommended (optimized) therapy. |
| Group B: Sacubitril/Valsartan | Experimental | Drug: Sacubitril-ValsartanSuspension of ACE inhibitors - for at least 36h of the last dose - or ARB. Initial dosage: Sacubitril/valsartan 49mg/51mg, 1 tablet twice daily. Target dose (after two weeks): 97mg/103 mg, 1 tablet twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Men or women, over 18;
- Diagnosed with resistant hypertension (using three or more antihypertensive agents of different classes - eg. angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blockers, loop and thiazide diuretics or potassium-sparing diuretics), at least 4 weeks before recruitment, with a BP that remains above the goal of 140/90 mmHg.
Key exclusion criteria (7 listed)
- Secondary and treatable hypertension;
- History of angioedema; significant cerebrovascular disease;
- Active liver disease (alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of the normal range and)
- Kidney dialysis or kidney transplantation or serum creatinine> 1.5 times the upper limit of the normal range or CrCl <30 mL/min;
- Previous or current diagnosis of heart failure;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril-ValsartanUse of sacubitril/valsartan after suspension of ACE inhibitors or ARBs. | Drug | Group B: Sacubitril/Valsartan |
Primary outcome
achieving the blood pressure target of <140/90mmg and the reducing of the mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), and mean sitting pulse pressure (msPP) over an 8-week period.
Time frame: 8 weeks
2 co-primary outcomes
Secondary efficacy outcomes included BP reduction stratified by Sac-Val dose compared to standard therapy.
Time frame: 8 weeks
Secondary outcome
1 secondary outcome
Secondary safety outcomes included incidence of acute myocardial infarction, hospitalization, stroke, hypotension, angioedema, electrolyte disturbances, CKD progression, and CV mortality
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacubitril-Valsartan in people with Resistant Hypertension and Blood Pressure, run by Hospital Geral Roberto Santos at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
achieving the blood pressure target of <140/90mmg and the reducing of the mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), and mean sitting pulse pressure (msPP) over an 8-week period. (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.