Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04458285
Recruitment Status : Recruiting
First Posted : July 7, 2020
Last Update Posted : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
ShuangXin Liu, 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.


Condition or disease Intervention/treatment Phase
Hemodialysis Complication Heart Failure Drug: Sacubitril / Valsartan Oral Tablet [Entresto] Drug: Benazepril 10mg Tablet Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


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.
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.
Other Name: LCZ696 100 mg tablet

Active Comparator: Benazepril
Patients in active comparator group will receive Benazepril with an dose of 10 mg once daily.
Drug: Benazepril 10mg Tablet
Patients in active comparator group will receive Benazepril with an dose of 10 mg once daily.




Primary Outcome Measures :
  1. Left ventricular ejection fraction (LVEF) [ Time Frame: 12 weeks ]
    Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study


Secondary Outcome Measures :
  1. 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.

  2. Left ventricular end diastolic volume (LVEDV) [ Time Frame: 12 weeks ]
    LVEDV is measured as baseline and after 12 weeks follow-up.

  3. Left atrial volume (LAV) [ Time Frame: 12 weeks ]
    LAV is measured as baseline and after 12 weeks follow-up.

  4. 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.

  5. Pulmonary Artery Pressure [ Time Frame: 12 weeks ]
    Pulmonary Artery Pressure is measured as baseline and after 12 weeks follow-up.

  6. 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.

  7. NYHA functional classification [ Time Frame: 12 weeks ]
    NYHA functional classification is assessed from baseline and 12 weeks follow-up.

  8. 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.

  9. Systolic and diastolic blood pressure [ Time Frame: 12 weeks ]
    Systolic and diastolic blood pressure will be measured every 2 weeks.

  10. Concentration of postassium [ Time Frame: 12 weeks ]
    Blood samples will be collected for analysis of concentration of postassium every 2 weeks.

  11. Electrocardiogram(ECG) [ Time Frame: 12 weeks ]
    ECG QT Interval analysis was performed at baseline and 12 weeks follow-up.

  12. Estimated glomerular filtration rate(eGFR) [ Time Frame: 12 weeks ]
    Change in estimated glomerular filtration rate(eGFR)

  13. Incidence of Angioedema [ Time Frame: 12 weeks ]
    Incidence of Angioedema during the study period 12 weeks.

  14. 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.


Other Outcome Measures:
  1. Neprilysin [ Time Frame: 12 weeks ]
    The concentration of Neprilysis is measured by Human Neprilysin ELISA Kit as baseline and after 12 weeks follow-up.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≤ 40%.
  • Mean sitting systolic blood pressure(msSBP)≥140 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04458285


Contacts
Layout table for location contacts
Contact: Faye Jiang, Doctor (+86)020-83525210 gdphgcp@gdph.org.cn

Locations
Layout table for location information
China, Guangdong
Guangdong Provincial People's Hospital Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Shuangxin Liu, Doctor    (+86)13543456446    13543456446@139.com   
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         
Sponsors and Collaborators
Guangdong Provincial People's Hospital
Investigators
Layout table for investigator information
Principal Investigator: Shuangxin Liu, Doctor Guangdong Provincial People's Hospital
Publications:
Layout table for additonal information
Responsible Party: ShuangXin Liu, Chief Physician, Guangdong Provincial People's Hospital
ClinicalTrials.gov Identifier: NCT04458285    
Other Study ID Numbers: 20191025
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ShuangXin Liu, Guangdong Provincial People's Hospital:
Sacubitril/valsartan
Benazepril
Hemodialysis
Heart failure
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Diseases
Cardiovascular Diseases
Valsartan
Benazepril
LCZ 696
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors