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

Heart Failure Clinical Trial

Official title:

The Effect of Sacubitril/Valsartan on Cardiovascular Events Outcome in Maintenance Dialysis Patients With Heart Failure and Efficacy Prediction of Baseline LVEF Value：A Prospective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04572724
• Other study ID #: 20200601054
• Status: Recruiting
• Phase: Phase 4
• Start date: July 6, 2020
• Est. completion date: June 2023

Study information

• Verified date: October 2020
• Source: Shenzhen Second People's Hospital
• Contact: YI XU
• Phone: +8613798309505
• Email: xuyi20001234[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 2023
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Hemodialysis Complication
• Peritoneal Dialysis Complication

Intervention

Drug:
• Sacubitril / Valsartan Oral Tablet
Sacubitril/Valsartan will start at 50mg bid, when blood pressure can be tolerable, the dose will be gradually increased to 100mg bid after taking for 2-4 weeks, and then the target dose is gradually add to the 200mg bid after another 2-4 weeks. Ensure BP>90/60mmHg, the minimum dose is 50mg bid if the patient can't tolerate higher dose but the blood pressure is stable at low dose.
• RAS Inhibitors
RAS inhibitor group allows the use of a monodose of any ACEi or ARB. Ensure BP>90/60mmHg, the minimum dose is half dose if the patient can't tolerate monodose but the blood pressure is stable at half dose.

Locations

Country	Name	City	State
China	Shenzhen Second People's Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Second People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cardiovascular events	death from any kinds of cardiovascular diseases	at least 18 months
Primary	hospitalization for heart failure	time from the day of enroll to a first unplanned hospitalization for heart failure	at least 18 months
Secondary	change rate of cardiovascular events	change rate of composite of death from cardiovascular diseases or a first unplanned hospitalization for heart failure	at least 18 months
Secondary	NT-proBNP	the change from baseline to 12 months in the NT-proBNP	12 months
Secondary	Kansas City Cardiomyopathy Questionnaire (KCCQ)	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.	1month, 6month,18 months