Sacubitril/Valsartan in Resistant Hypertension

NCT ID: NCT04637152

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-11
• Study Completion Date: 2022-08-17

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.

Conditions

Resistant Hypertension; Blood Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group A: Usual recommended therapy

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Sacubitril-Valsartan

Intervention Type: DRUG

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

Interventions

Sacubitril-Valsartan

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Geral Roberto Santos

OTHER

Sponsor Role: lead

Hospital Universitário Professor Edgard Santos

OTHER

Sponsor Role: collaborator

Responsible Party

Andre Rodrigues Duraes

Medical Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

General Hospital Roberto Santos

Salvador, Estado de Bahia, Brazil

Hospital Universitário Professor Edgard Santos

Salvador, Estado de Bahia, Brazil

Countries

Brazil

Other Identifiers

HGeralRobertoSantos

Identifier Type: -

Identifier Source: org_study_id