Clinical trial NCT04458285: Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hemodialysis Complication
Heart Failure
Keywords: Sacubitril/valsartan
valsartan
Hemodialysis
Heart failure
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2020-07-07
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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 ≤ 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.

Primary outcomes:
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 12 weeks
Secondary outcomes:
measure: N terminal pro B type natriuretic peptide (NT-prpBNP)
timeFrame: 12 weeks
measure: Left ventricular end diastolic volume (LVEDV)
timeFrame: 12 weeks
measure: Left atrial volume (LAV)
timeFrame: 12 weeks
measure: The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E')
timeFrame: 12 weeks
measure: Pulmonary Artery Pressure
timeFrame: 12 weeks
measure: Concentration of high-sensitivity serum troponin T
timeFrame: 12 weeks
measure: NYHA functional classification
timeFrame: 12 weeks
measure: Minnesota Heart Failure Quality of Life Questionnaire (LiHFe)
timeFrame: 12 weeks
measure: Systolic and diastolic blood pressure
timeFrame: 12 weeks
measure: Concentration of postassium
timeFrame: 12 weeks
measure: Electrocardiogram(ECG)
timeFrame: 12 weeks
measure: Estimated glomerular filtration rate(eGFR)
timeFrame: 12 weeks
measure: Incidence of Angioedema
timeFrame: 12 weeks
measure: Concentration of alanine aminotransferase or aspartate aminotransferase
timeFrame: 12 weeks
Other outcomes:
measure: Neprilysin
timeFrame: 12 weeks
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Shuangxin Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.