The Effect of Sacubitril/Valsartan on Cardiovascular Events in Dialysis Patients and Efficacy Prediction of Baseline LVEF Value

Phase 4

• Conditions: Peritoneal Dialysis Complication; Heart Failure; Hemodialysis Complication
• Interventions: Drug: RAS Inhibitors; Drug: Sacubitril / Valsartan Oral Tablet

• Registration Number: NCT04572724
• Lead Sponsor: Shenzhen Second People's Hospital

Brief Summary

Patients with end stage renal disease (ESRD), especially after having maintenance dialysis are among the highest risk of heart failure (HF), which is the most important cause that affects survival rate and quality of life. Sacubitril/Valsartan is recommended as a first-line option for treating symptomatic chronic heart failure, especially HF with reduced ejection fraction (HFrEF). Sacubitril/Valsartan was reported the different effectiveness in HFrEF and HF with preserved ejection fraction (HFpEF), and the clinical trials' results are controversial in HFpEF patients. So far, there have been seven clinical trials (or subgroups of trials) that used sacubitril/valsartan in heart failure patients with chronic kidney disease, only one retrospective study to evaluate the improvement of cardiovascular biomarkers and LVEF in hemodialysis patients who have HFrEF. In addition, there is no article predicting the outcomes of Sacubitril/Valsartan, the inclusion criteria of LVEF value are not consistent. Investigators will perform a prospective, cohort study to evaluate the efficacy and safety of Sacubitril/Valsartan on Cardiovascular Events Outcome in Maintenance hemodialysis and peritoneal dialysis patients with Heart Failure, and use secondary analysis to find out the range of baseline LVEF Value to predict the therapeutic effects.

Detailed Description

The trial will examine the effect of Sacubitril/Valsartan on cardiovascular events in HF patients receiving maintenance hemodialysis or peritoneal dialysis. Subjects will be divided into two groups (1:1 matching will be achieved after a screening of propensity score) to receive one of two interventions in addition to standard HF management: Sacubitril/Valsartan group or RAAS inhibitor group. All subjects can have a beta-blocker, CCB, and/or alpha-blockers to control BP. Dialysis treatment: patients normally complete hemodialysis or peritoneal dialysis, need to ensure adequate dialysis requirements, no obvious overload, patients achieve dry weight after dialysis.

Participants will be treated and follow-up for at least 18 months.

Study Timeline

• Study Start: 2020-07-06
• Study First Submitted: 2020-09-28
• Study First Submitted QC: 2020-09-28
• Status Verified: 2020-10
• Study First Posted: 2020-10-01
• Last Update Submitted: 2020-10-03
• Last Update Posted: 2020-10-08
• Primary Completion: 2022-11
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• 18 to 70 years old participants, No restrictions on gender or race
• Stable heart failure in New York Heart Association (NYHA) class II, III, or IV symptoms, presentation of typical heart failure symptoms accompanied by HF signs caused by a structural and/or functional cardiac abnormality
• Under maintenance dialysis (hemodialysis or peritoneal dialysis) for more than one year
• Patients have a plasma N-terminal pro-BNP (NT-proBNP) level ≥600 pg per milliliter, or if they had been hospitalized for heart failure within the previous 12 months, an NT-proBNP ≥400 pg per milliliter
• Patients written informed consent

Exclusion Criteria

• Repeatedly symptomatic hypotension, systolic blood pressure of less than 90 mmHg and diastolic blood pressure of less than 60 mmHg, which cannot tolerate the RASS inhibitors therapy
• Patients who have significant fluid overload and did not reach dry weight stably
• Patients with acute myocardial infarction or implantation of intracoronary stents, coronary artery bypass grafting (CABG) and pacemaker within three months
• Patients with special type of heart disease, including cardiac amyloidosis, congential heart disease and pericardial disease
• Patients with malignant hypertension and hypertensive emergencies that can not be controlled
• Patients with significant impaired liver function
• Patients with repeatedly or server infection
• Allergic to the trial drugs
• Unacceptable side effects during receipt of RASS inhibitors
• Pregnancy
• Patients who are unable to provide informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RAS inhibitor treatment group	RAS Inhibitors	RAS inhibitor group allows the use of a monodose of any ACEi or ARB. All subjects can have a beta-blocker, CCB, and/or alpha-blockers to control BP. Dialysis treatment: patients normally complete hemodialysis or peritoneal dialysis, need to ensure adequate dialysis requirements, no obvious overload, patients achieve dry weight after dialysis.
Sacubitril/Valsartan treatment group	Sacubitril / Valsartan Oral Tablet	Sacubitril/Valsartan will be administered step by step with a titrated dose. When patients switching to Sacubitril/Valsartan from RAS inhibitor, a washout period of at least 36 hours is required to decrease the risk of angioedema. All subjects can have a beta-blocker, CCB, and/or alpha-blockers to control BP. Dialysis treatment: patients normally complete hemodialysis or peritoneal dialysis, need to ensure adequate dialysis requirements, no obvious overload, patients achieve dry weight after dialysis.

Primary Outcome Measures

Name	Time	Method
hospitalization for heart failure	at least 18 months	time from the day of enroll to a first unplanned hospitalization for heart failure
cardiovascular events	at least 18 months	death from any kinds of cardiovascular diseases

Secondary Outcome Measures

Name	Time	Method
NT-proBNP	12 months	the change from baseline to 12 months in the NT-proBNP
change rate of cardiovascular events	at least 18 months	change rate of composite of death from cardiovascular diseases or a first unplanned hospitalization for heart failure
Kansas City Cardiomyopathy Questionnaire (KCCQ)	1month, 6month,18 months	the change from baseline to 1month, 6month,18 months in the clinical summary score on the Kansas City Cardiomyopathy Questionnaire (KCCQ)25 (on a scale from 0 to 100, with higher scores indicating fewer symptoms and physical limitations associated with heart failure).The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL) within a 2-week recall period. It is an important prognostic variable in cardiovascular disease.

Trial Locations

Locations (1)

Shenzhen Second People's Hospital; 🇨🇳 Shenzhen, Guangdong, China