Clinical trial NCT04637152: Sacubitril/Valsartan in Resistant Hypertension
Official title: Anti-Hypertensive Effect of Sacubitril/Valsartan in Resistant Hypertension: Randomized Clinical Trial - The HEVA Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Resistant Hypertension
Blood Pressure
Keywords: Resistant Hypertension
LCZ696
Blood pressure control
sacubitril/valsartan
Lead sponsor: Hospital Geral Roberto Santos
Sponsor class: OTHER
Collaborators: name: Hospital Universitário Professor Edgard Santos
First posted: 2020-11-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: It was adopted an equal allocation of patients to each treatment (i.e., 1:1 randomization)
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
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.
timeFrame: 8 weeks
measure: Secondary efficacy outcomes included BP reduction stratified by Sac-Val dose compared to standard therapy.
timeFrame: 8 weeks
Secondary outcomes:
measure: Secondary safety outcomes included incidence of acute myocardial infarction, hospitalization, stroke, hypotension, angioedema, electrolyte disturbances, CKD progression, and CV mortality
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: General Hospital Roberto Santos
state: Bahia
city: Salvador
country: Brazil
facility: Hospital Universitário Professor Edgard Santos
state: Bahia
Study officials:
References: