Sacubitril/Valsartan in Resistant Hypertension (HEVA)

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.

Study Overview

• Status: Unknown
• Conditions: Blood Pressure; Resistant Hypertension
• Intervention / Treatment: Drug: Sacubitril-Valsartan

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40301-110
      • Recruiting
      • General Hospital Roberto Santos
      • Contact: Andre R Duraes, M.D, PhD; Phone Number: 71991888399; Email: andreduraes@gmail.com
      • Principal Investigator: Andre R Duraes, M.D, PhD
    • Salvador, Bahia, Brazil, 40301-155
      • Recruiting
      • Hospital Universitario Professor Edgard Santos
      • Contact: Roque A Junior, M.D, PhD; Phone Number: 71981767863; Email: roque.aras@uol.com.br
      • Principal Investigator: Yasmin SL Bitar, B.S
      • Sub-Investigator: Cristiano Ricardo B de Macedo, M.D, PhD
      • Principal Investigator: Roque A Junior, M.D, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in systolic blood pressure and diastolic blood pressure in the sitting position.	The mean reduction in systolic blood pressure and diastolic blood pressure in the sitting position	12 weeks
Mean reduction in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure	The mean reduction in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcomes	Rate of hypotension, angioedema, uncontrolled blood pressure above 220x120, relevant hydroelectrolytic disorders, hospitalization, stroke and other cardiovascular events.	12 weeks

Collaborators and Investigators

• Sponsor: Hospital Geral Roberto Santos
• Collaborators: Hospital Universitário Professor Edgard Santos

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Anticipated): October 11, 2022
• Study Completion (Anticipated): November 11, 2022

Study Registration Dates

• First Submitted: November 14, 2020
• First Submitted That Met QC Criteria: November 14, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 27, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Resistant Hypertension; Blood pressure control; LCZ696; sacubitril/valsartan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: HGeralRobertoSantos

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No