Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure (ESARHD-HF)

October 4, 2020 updated by: ShuangXin Liu, Guangdong Provincial People's Hospital

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

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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

118

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Recruiting
        • Guangdong Provincial People's Hospital
        • Contact:
        • Principal Investigator:
          • Shuangxin Liu, Doctor
        • Sub-Investigator:
          • Li Zhang, Doctor
        • Sub-Investigator:
          • Zhonglin Feng, Master
        • Sub-Investigator:
          • Sijia Li, Master
        • Sub-Investigator:
          • Zhuo Li, Master
        • Sub-Investigator:
          • Feng Wen, Doctor
        • Sub-Investigator:
          • Lei Fu, Master
        • Sub-Investigator:
          • Jianchao Ma, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sacubitril/valsartan
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.
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.
Other Names:
  • LCZ696 100 mg tablet
Active Comparator: Valsartan
Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.
Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction (LVEF)
Time Frame: 12 weeks
Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study
12 weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neprilysin
Time Frame: 12 weeks
The concentration of Neprilysis is measured by Human Neprilysin ELISA Kit as baseline and after 12 weeks follow-up.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Shuangxin Liu, Doctor, Guangdong Provincial People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Anticipated)

December 31, 2020

Study Completion (Anticipated)

December 31, 2020

Study Registration Dates

First Submitted

June 26, 2020

First Submitted That Met QC Criteria

July 2, 2020

First Posted (Actual)

July 7, 2020

Study Record Updates

Last Update Posted (Actual)

October 6, 2020

Last Update Submitted That Met QC Criteria

October 4, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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