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

Heart Failure Clinical Trial

— ESARHD-HF  

Official title:

A Multi-center, Randomized, Open-label, Active-controlled, 12-week Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04458285
• Other study ID #: 20191025
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2020
• Est. completion date: December 31, 2020

Study information

• Verified date: July 2020
• Source: Guangdong Provincial People's Hospital
• Contact: Faye Jiang, Doctor
• Phone: (+86)020-83525210
• Email: gdphgcp[@]gdph.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 118
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Heart Failure
• Hemodialysis Complication

Intervention

Drug:
• Sacubitril / Valsartan Oral Tablet [Entresto]
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.
• Valsartan 80mg Tablet
Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

Locations

Country	Name	City	State
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Provincial People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. Erratum in: N Engl J Med. 2019 Mar 14;380(11):1090. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neprilysin	The concentration of Neprilysis is measured by Human Neprilysin ELISA Kit as baseline and after 12 weeks follow-up.	12 weeks
Primary	Left ventricular ejection fraction (LVEF)	Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study	12 weeks
Secondary	N terminal pro B type natriuretic peptide (NT-prpBNP)	Blood samples will be collected for analysis of concentration of N terminal pro B type natriuretic peptide (NT-proBNP) every 2 weeks.	12 weeks
Secondary	Left ventricular end diastolic volume (LVEDV)	LVEDV is measured as baseline and after 12 weeks follow-up.	12 weeks
Secondary	Left atrial volume (LAV)	LAV is measured as baseline and after 12 weeks follow-up.	12 weeks
Secondary	The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E')	E/E' is measured as baseline and after 12 weeks follow-up.	12 weeks
Secondary	Pulmonary Artery Pressure	Pulmonary Artery Pressure is measured as baseline and after 12 weeks follow-up.	12 weeks
Secondary	Concentration of high-sensitivity serum troponin T	Blood samples will be collected for analysis of concentration of serum troponin every 4 weeks.	12 weeks
Secondary	NYHA functional classification	NYHA functional classification is assessed from baseline and 12 weeks follow-up.	12 weeks
Secondary	Minnesota Heart Failure Quality of Life Questionnaire (LiHFe)	Change in health status is assessed using the disease-specific Minnesota Heart Failure Quality of Life Questionnaire.	12 weeks
Secondary	Systolic and diastolic blood pressure	Systolic and diastolic blood pressure will be measured every 2 weeks.	12 weeks
Secondary	Concentration of postassium	Blood samples will be collected for analysis of concentration of postassium every 2 weeks.	12 weeks
Secondary	Electrocardiogram(ECG)	ECG QT Interval analysis was performed at baseline and 12 weeks follow-up.	12 weeks
Secondary	Estimated glomerular filtration rate(eGFR)	Change in estimated glomerular filtration rate(eGFR)	12 weeks
Secondary	Incidence of Angioedema	Incidence of Angioedema during the study period 12 weeks.	12 weeks
Secondary	Concentration of alanine aminotransferase or aspartate aminotransferase	Blood samples will be collected for analysis of concentration of alanine aminotransferase or aspartate aminotransferase every 2 weeks.	12 weeks