Effects and Safety of Sacubitril/Valsartan on Refractory Hypertension

NCT05545059 | Unknown Phase 3

• 1 other identifier: 2020-KY-126
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

Resistant hypertension (RH) accounted for a considerable proportion of patients with hypertension. It has been revealed to impose certain adverse effects on the prognosis of patients with cardiovascular diseases. The antihypertensive effect of sacubitril/valsartan being fully confirmed in previous studies, there were no related randomized controlled trials (RCT) about this potency among Chinese patients with RH. The investigators designed this study to evaluated effects and safety of sacubitril/valsartan versus valsartan on Chinese patients with RH.

Conditions

Resistant Hypertension

Keywords

Resistant hypertension; ambulatory blood pressure; sacubitril/valsartan; valsartan

Outcome Measures

Primary Outcomes (1)

• the change in 24 hours average ambulatory systolic pressure from baseline to 8 weeks after randomization

  the change in 24 hours average ambulatory systolic blood pressure (in mmHg) from baseline to 8 weeks after randomization

  8 weeks after randomization

Secondary Outcomes (19)

• Change in 24 hours average ambulatory diastolic blood pressure, daytime and night-time blood pressure and office blood pressure

  8 weeks after randomization

• Change in level of cardiac marker reflecting the heart failure

  8 weeks after randomization

• Change in level of cardiac marker reflecting myocardial damage

  8 weeks after randomization

• Change in level of novel cardiac marker reflecting the heart failure

  8 weeks after randomization

• Change in level of cardiac marker reflectting myocardial metabolism

  8 weeks after randomization

Study Arms (2)

sacubitril/valsartan group

EXPERIMENTAL

The experimental group will be sacubitril/valsartan group. Patients assigned to this group will receive sacubitril/valsartan 200mg added to existing medication regimens before randomization including amlodipine 10mg per day, hydrochlorothiazide 25 mg per day, spironolactone 20 mg per day. The initial dose of sacubitril/valsartan will be 100mg per day and will be doubled to 200mg per day after 2 weeks then maintain until the end of the 8-week treatment period.

Drug: Sacubitril/valsartan

valsartan group

ACTIVE COMPARATOR

The control group will be valsartan group, which patients will receive valsartan 160mg added to existing medication regimens before randomization including amlodipine 10mg per day, hydrochlorothiazide 25 mg per day, spironolactone 20 mg per day. The initial dose of valsartan will be 80mg per day and will be doubled to 160mg per day 2 weeks later and then maintain until the end of the 8-week treatment period.

Drug: valsartan

Interventions

Sacubitril/valsartan DRUG

In sacubitril/valsartan group, patients will receive amlodipine 10mg, hydrochlorothiazide 25 mg, spironolactone 20 mg, sacubitril/valsartan 200mg to treat. The initial dose of sacubitril/valsartan will be 100mg per day and will be doubled to 200mg per day after 2 weeks then maintain until the end of the 8-week treatment period.

Also known as: amlodipine 10mg, hydrochlorothiazide 25 mg, spironolactone 20 mg

sacubitril/valsartan group

valsartan DRUG

In valsartan group, patients will receive amlodipine 10mg, hydrochlorothiazide 25 mg, spironolactone 20 mg and valsartan 160mg. The initial dose of valsartan will be 80mg per day and will be doubled to 160mg per day 2 weeks later and then maintain until the end of the 8-week treatment period.

Also known as: amlodipine 10mg, hydrochlorothiazide 25 mg, spironolactone 20 mg

valsartan group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of resistant hypertension
• ≥18 and ≤75 years old at the time of randomization
• Must agree to comply with all requirements and sign the informed consent form

You may not qualify if:

• unwilling to sign informed consent.
• Severe renal insufficiency
• Research related drug contraindications
• secondary hypertension
• Cardiovascular event
• Persistent arrhythmia, valvular heart disease, and class III-IV heart failure or left ventricular ejection fraction \<45%.
• Severe liver function impairment (Child-Pugh C), biliary cirrhosis and/or cholestasis
• History of angioedema and asthma
• Woman of childbearing age who do not take effective contraceptive measures or pregnant or breastfeeding
• Allergic to drugs related to the study
• Suffering from serious tumor-related diseases, receives tumor-related treatment, or has a life expectancy of less than 2 years
• Planning to join other clinical trials
• Anticipated changes in medical conditions
• Need to take study-related drugs for reasons other than hypertension
• Suffering from other diseases that may prevent the patient from participating fully period of the study

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

Related Publications (5)

• Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008 Jun 24;117(25):e510-26. doi: 10.1161/CIRCULATIONAHA.108.189141.

  PMID: 18574054 BACKGROUND

• Lamirault G, Artifoni M, Daniel M, Barber-Chamoux N, Nantes University Hospital Working Group On Hypertension. Resistant Hypertension: Novel Insights. Curr Hypertens Rev. 2020;16(1):61-72. doi: 10.2174/1573402115666191011111402.

  PMID: 31622203 BACKGROUND

• Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016 Mar 5;387(10022):957-967. doi: 10.1016/S0140-6736(15)01225-8. Epub 2015 Dec 24.

  PMID: 26724178 BACKGROUND

• Kario K, Shin J, Chen CH, Buranakitjaroen P, Chia YC, Divinagracia R, Nailes J, Hoshide S, Siddique S, Sison J, Soenarta AA, Sogunuru GP, Tay JC, Teo BW, Turana Y, Zhang Y, Park S, Van Minh H, Wang JG. Expert panel consensus recommendations for ambulatory blood pressure monitoring in Asia: The HOPE Asia Network. J Clin Hypertens (Greenwich). 2019 Sep;21(9):1250-1283. doi: 10.1111/jch.13652.

  PMID: 31532913 BACKGROUND

• Kario K, Sun N, Chiang FT, Supasyndh O, Baek SH, Inubushi-Molessa A, Zhang Y, Gotou H, Lefkowitz M, Zhang J. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study. Hypertension. 2014 Apr;63(4):698-705. doi: 10.1161/HYPERTENSIONAHA.113.02002. Epub 2014 Jan 20.

  PMID: 24446062 BACKGROUND

MeSH Terms

Interventions

sacubitril and valsartan sodium hydrate drug combination; Amlodipine; Hydrochlorothiazide; Spironolactone; Valsartan

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Tetrazoles; Azoles; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Dengfeng Geng, Dr.

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dengfeng Geng, Dr.

CONTACT

020-81332623; dr.dfengg@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: September 19, 2022
• Study Start: September 24, 2022
• Primary Completion: October 28, 2022
• Study Completion: March 31, 2023
• Last Updated: September 19, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)