- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04458285
Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure (ESARHD-HF)
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
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Faye Jiang, Doctor
- Phone Number: (+86)020-83525210
- Email: gdphgcp@gdph.org.cn
Study Locations
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Guangdong
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Guangzhou, Guangdong, China, 510080
- Recruiting
- Guangdong Provincial People's Hospital
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Contact:
- Shuangxin Liu, Doctor
- Phone Number: (+86)13543456446
- Email: 13543456446@139.com
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Principal Investigator:
- Shuangxin Liu, Doctor
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Sub-Investigator:
- Li Zhang, Doctor
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Sub-Investigator:
- Zhonglin Feng, Master
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Sub-Investigator:
- Sijia Li, Master
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Sub-Investigator:
- Zhuo Li, Master
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Sub-Investigator:
- Feng Wen, Doctor
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Sub-Investigator:
- Lei Fu, Master
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Sub-Investigator:
- Jianchao Ma, Doctor
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
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Active Comparator: Valsartan
Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.
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Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.
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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.
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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
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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
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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
Investigators
- Principal Investigator: Shuangxin Liu, Doctor, Guangdong Provincial People's Hospital
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20191025
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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