Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure

NCT04458285 | Unknown DMC

• 1 other identifier: 20191025
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, and has been recently indicated as a new treatment option with a strong level of recommendation (class I, level of evidence B) in the main international guidelines. Cardiovascular disease (CVD) is the most common cause of death in end stage renal disease (ESRD) patients undergoing hemodialysis (HD). Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. So far, no data available about the efficacy and safety of sacubitril/valsartan in ESRD patients undergoing hemodialysis, although this medication was noted to be effective and comparably well tolerable in those with estimated glomerular filtration rate(eGFR) 20 to 60 mL/min/1.73 m2 in the United Kingdom Heart and Renal Protection-III trial. The purpose of this open label, randomized controlled study with prospective data collection is to assess the efficacy and safety of sacubitril/valsartan in maintenance hemodialysis patients with heart failure.

Conditions

Hemodialysis Complication; Heart Failure

Keywords

Sacubitril/valsartan; valsartan; Hemodialysis; Heart failure

Outcome Measures

Primary Outcomes (1)

• Left ventricular ejection fraction (LVEF)

  Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study

  12 weeks

Secondary Outcomes (14)

• N terminal pro B type natriuretic peptide (NT-prpBNP)

  12 weeks

• Left ventricular end diastolic volume (LVEDV)

  12 weeks

• Left atrial volume (LAV)

  12 weeks

• The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E')

  12 weeks

• Pulmonary Artery Pressure

  12 weeks

Other Outcomes (1)

• Neprilysin

  12 weeks

Study Arms (2)

Sacubitril/valsartan

EXPERIMENTAL

Patients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous angiotensin converting enzyme inhibitor(ACEI), ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks.

Drug: Sacubitril / Valsartan Oral Tablet [Entresto]

Valsartan

ACTIVE COMPARATOR

Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

Drug: Valsartan 80mg Tablet

Interventions

Sacubitril / Valsartan Oral Tablet [Entresto] DRUG

Patients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous ACEI, ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks.

Also known as: LCZ696 100 mg tablet

Sacubitril/valsartan

Valsartan 80mg Tablet DRUG

Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

Valsartan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained before any study assessment is performed.
• End stage renal disease (ESRD) patients (eGFR\<15ml/min/1.73m² as measured by the Chronic Kidney Disease Epidemiology Collaboration formula at screening) who have been receiving hemodialysis 3 times a week for at least 12 weeks before registration.
• Chronic heart failure (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 50%.
• Mean sitting systolic blood pressure(msSBP)≥110 mmHg.
• Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker for at least 2 weeks.
• Good compliance.

You may not qualify if:

• Acute renal failure with hemodialysis.
• Isolated right heart failure owing to pulmonary disease, primary cause of dyspnea due to noncardiac, non-HF causes such as acute or chronic respiratory disorders.
• Systolic blood pressure lower than 100 mmHg at screening (\<95 mmHg at the randomization visit).
• Previous history of intolerance to recommended target doses of angiotensin receptor blockers.
• Significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy (such as serum potassium\>5.5 or \<3.5mmol/L, serum sodium\<130mmol/L or alanine aminotransferase or aspartate aminotransferase\>2 times the upper limit of the normal range)
• History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes.
• History of angioedema.
• Any medications that have potential for drug-drug interaction with LCZ696 will not be allowed during the study.
• Pregnant female.
• Use of sacubitril/valsartan prior to week-2.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (3)

• McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.

  PMID: 25176015 BACKGROUND

• Haynes R, Judge PK, Staplin N, Herrington WG, Storey BC, Bethel A, Bowman L, Brunskill N, Cockwell P, Hill M, Kalra PA, McMurray JJV, Taal M, Wheeler DC, Landray MJ, Baigent C. Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease. Circulation. 2018 Oct 9;138(15):1505-1514. doi: 10.1161/CIRCULATIONAHA.118.034818.

  PMID: 30002098 BACKGROUND

• Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.

  PMID: 30415601 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril; Valsartan; sacubitril and valsartan sodium hydrate drug combination; Tablets

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Shuangxin Liu, Doctor

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Faye Jiang, Doctor

CONTACT

(+86)020-83525210; gdphgcp@gdph.org.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 7, 2020
• Study Start: January 1, 2020
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: October 6, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)