HEVA: Sacubitril/Valsartan in Resistant Hypertension

Sponsor

Hospital Geral Roberto Santos (Other)

Overall Status

Recruiting

CT.gov ID

NCT04637152

Collaborator

Hospital Universitário Professor Edgard Santos (Other)

100

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Resistant Hypertension Blood Pressure	Drug: Sacubitril-Valsartan	Phase 2

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

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)

Masking:

Single (Investigator)

Masking Description:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

Anti-Hypertensive Effect of Sacubitril/Valsartan in Resistant Hypertension: Randomized Clinical Trial - The HEVA Study

Actual Study Start Date :

Nov 11, 2020

Anticipated Primary Completion Date :

Oct 11, 2022

Anticipated Study Completion Date :

Nov 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Group A: Usual recommended therapy Antihypertensive regimen based on the usual recommended (optimized) therapy.
Experimental: Group B: Sacubitril/Valsartan 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.	Drug: Sacubitril-Valsartan Use of sacubitril/valsartan after suspension of ACE inhibitors or ARBs.

Arm

Intervention/Treatment

No Intervention: Group A: Usual recommended therapy

Antihypertensive regimen based on the usual recommended (optimized) therapy.

Experimental: Group B: Sacubitril/Valsartan

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.

Drug: Sacubitril-Valsartan

Use of sacubitril/valsartan after suspension of ACE inhibitors or ARBs.

Outcome Measures

Primary Outcome Measures

Reduction in systolic blood pressure and diastolic blood pressure in the sitting position. [12 weeks]
The mean reduction in systolic blood pressure and diastolic blood pressure in the sitting position
Mean reduction in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure [12 weeks]
The mean reduction in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP)

Secondary Outcome Measures

Safety outcomes [12 weeks]
Rate of hypotension, angioedema, uncontrolled blood pressure above 220x120, relevant hydroelectrolytic disorders, hospitalization, stroke and other cardiovascular events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.