Sacubitril/Valsartan Versus Amlodipine in Hypertension and Left Ventricular Hypertrophy.

NCT04929600 | Unknown Phase 4 DMC

• 1 other identifier: PARASTRAIN
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Study name: Prospective Comparison of Angiotensin receptor neprilysin inhibitor (ARNI) with Amlodipine on ventricular remodeling in hypertension and left ventricular hypertrophy.
2. 2.Medicine: sacubitril/valsartan (ARNI, 200mg tablet) and the matching placebo; amlodipine (5mg tablet) and the matching placebo.
3. 3.Rationale: according to the results of previous clinical studies, ARNI has obvious advantages in improving cardiac remodeling and reducing blood pressure. However, there is no evidence to demonstrate the efficacy of ARNI in reducing blood pressure and improving ventricular remodeling in hypertension patients with left ventricular hypertrophy (LVH) compared with calcium channel blockers.
4. 4.Objective: to demonstrate the superior efficacy of ARNI on improvement of LVH and blood pressure control compared with amlodipine in hypertension patients with LVH.
5. 5.Study design: This study This is a 24-week prospective, randomized, active-controlled, double-blind, multi-center study, with two equally sized treatment groups: sacubitril/valsartan (200mg tablet); amlodipine (5mg tablet).
6. 6.Study population: men or women aged over 18 years; Untreated patients or patients with taking single antihypertensive drugs; Essential mild to moderate hypertension; Echocardiographic diagnosis of LVH.
7. 7.Randomization and treatment: Eligible patients will be randomly divided into 2 groups, taking one pill of sacubitril/valsartan (200mg tablet) + one pill of matching placebo of amlodipine daily, or one pill of amlodipine (5 mg/tablet) + one pill of matching placebo of sacubitril/valsartan daily.
8. 8.Follow up: after meeting the inclusion criteria, there will be 2-week placebo run-in. Then patients will be randomly assigned into ARNI group and amlodipine group. There will be 5 visiting points in the treatment period, which will be the 4th week, 8th week, 12th week, 18th week and 24th week.
9. 9.Sample size: 120 patients in total.
10. 10.Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in April 2021, recruitment will start. Patients enrollment and follow-up will be performed between June 2021 to June 2022.

Conditions

Hypertension; Left Ventricular Hypertrophy

Keywords

sacubitril/valsartan; amlodipine; blood pressure; global longitudinal strain

Outcome Measures

Primary Outcomes (1)

• Change in LVGLS after 24 weeks

  Change in left ventricular global longitudinal strain (LVGLS) after 24-week treatments. At baseline and 24-week follow-up, all patients will undergo standard transthoracic echocardiography performed in the sinus rhythm using the Vivid E9 and E95 Echo-system (General Electric Medical Health, Milwaukee, Wisconsin, USA) equipped with a M5S transducer. LVGLS will be obtained from two-, three-, and four-chamber apical views, and LVGLS analysis will be performed using an offline software (EchoPac, Version 113; General Electric Medical Health).

  Baseline and 24 weeks

Secondary Outcomes (5)

• Change in LVGLS after 12 weeks

  Baseline and 12 weeks

• Changes in LVMI after 24 weeks

  Baseline and 24 weeks

• Changes in LVMI after 12 weeks

  Baseline and 12 weeks

• Blood pressure after 24 weeks

  Baseline and 24 weeks

• Blood pressure after 12 weeks

  Baseline and 12 weeks

Study Arms (2)

Experimental

EXPERIMENTAL

One pill of sacubitril/valsartan (200mg tablet) + one pill of matching placebo of amlodipine daily. If possible, dosage titration should be conducted.

Drug: sacubitril/valsartan

Comparator

ACTIVE COMPARATOR

One pill of amlodipine (5mg tablet) + one pill of matching placebo of sacubitril/valsartan daily. If possible, dosage titration should be conducted.

Drug: Amlodipine

Interventions

sacubitril/valsartan DRUG

Sacubitril/valsartan oral tablets (200mg) one pill a day + matching placebo of amlodipine one pill a day.

Experimental

Amlodipine DRUG

Amlodipine oral tablets (5mg) one pill a day + matching placebo of sacubitril/valsartan one pill a day.

Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18;
• Essential mild to moderate hypertension (office systolic blood pressure (SBP) ≥ 140 and \< 180mmHg in untreated patients or patients with taking single antihypertensive drugs (not including single-pill combination))；
• Echocardiographic diagnosis of LVH，LVMI: male≥115g/m2, female≥ 95g/m2;
• Ability to understand the study requirements and provide informed consent.

You may not qualify if:

• Hypersensitivity history to any study drug or similar drug (ARB, ACEI, neprilysin inhibitor；
• Severe renal insufficiency (eGFR \< 30 mL/min/1.73m2);
• Hyperkalemia (serum potassium \> 5mmol/L);
• Active liver disease or hepatic insufficiency (AST or ALT \> 3 times upper limit of normal);
• History of malignancy over the past 5 years;
• Severe disease patients with life expectancy of \< 1 year;
• Previous or current diagnosis of heart failure;
• Stroke or myocardial infarction within 6 months;
• Previous or current atrial fibrillation, frequent ventricular premature beats, supraventricular tachycardia;
• Patients who are receiving other study drugs or study medical devices;
• Pregnant or lactating women;
• Other circumstances that patients are not appropriate for the study upon the investigator's judgment.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai Institite of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200025, China

RECRUITING

MeSH Terms

Conditions

Hypertension; Hypertrophy, Left Ventricular

Interventions

sacubitril and valsartan sodium hydrate drug combination; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cardiomegaly; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients in ARNI group will take sacubitril/valsartan + matching placebo of amlodipine; Patients in amlodipine group will take amlodipine + matching placebo of sacubitril/valsartan. Any markers that can identify placebo or active drugs will be removed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Shanghai Institute of Hypertension

Model Details: After screening and run-in period, eligible patients will be randomly assigned into ARNI group (sacubitril/valsartan 200-400mg QD) or amlodipine group (amlodipine 5-10mg QD).

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: June 18, 2021
• Study Start: November 28, 2021
• Primary Completion: June 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (1)