Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure
- Conditions
- Hemodialysis ComplicationHeart Failure
- Interventions
- Registration Number
- NCT04458285
- Lead Sponsor
- Guangdong Provincial People's Hospital
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 118
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sacubitril/valsartan Sacubitril / Valsartan Oral Tablet [Entresto] 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. Valsartan Valsartan 80mg Tablet Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.
- Primary Outcome Measures
Name Time Method Left ventricular ejection fraction (LVEF) 12 weeks Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study
- Secondary Outcome Measures
Name Time Method Concentration of high-sensitivity serum troponin T 12 weeks Blood samples will be collected for analysis of concentration of serum troponin every 4 weeks.
Concentration of postassium 12 weeks Blood samples will be collected for analysis of concentration of postassium every 2 weeks.
Minnesota Heart Failure Quality of Life Questionnaire (LiHFe) 12 weeks Change in health status is assessed using the disease-specific Minnesota Heart Failure Quality of Life Questionnaire.
Systolic and diastolic blood pressure 12 weeks Systolic and diastolic blood pressure will be measured every 2 weeks.
N terminal pro B type natriuretic peptide (NT-prpBNP) 12 weeks Blood samples will be collected for analysis of concentration of N terminal pro B type natriuretic peptide (NT-proBNP) every 2 weeks.
Left atrial volume (LAV) 12 weeks LAV is measured as baseline and after 12 weeks follow-up.
Electrocardiogram(ECG) 12 weeks ECG QT Interval analysis was performed at baseline and 12 weeks follow-up.
Estimated glomerular filtration rate(eGFR) 12 weeks Change in estimated glomerular filtration rate(eGFR)
Incidence of Angioedema 12 weeks Incidence of Angioedema during the study period 12 weeks.
Left ventricular end diastolic volume (LVEDV) 12 weeks LVEDV is measured as baseline and after 12 weeks follow-up.
The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E') 12 weeks E/E' is measured as baseline and after 12 weeks follow-up.
Pulmonary Artery Pressure 12 weeks Pulmonary Artery Pressure is measured as baseline and after 12 weeks follow-up.
NYHA functional classification 12 weeks NYHA functional classification is assessed from baseline and 12 weeks follow-up.
Concentration of alanine aminotransferase or aspartate aminotransferase 12 weeks Blood samples will be collected for analysis of concentration of alanine aminotransferase or aspartate aminotransferase every 2 weeks.
Trial Locations
- Locations (1)
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China