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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Hemodialysis Complication; Peritoneal Dialysis Complication
• Intervention / Treatment: Drug: Sacubitril / Valsartan Oral Tablet; Drug: RAS Inhibitors

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yi Xu; Phone Number: +8613798309505; Email: xuyi20001234@163.com
• Study Contact Backup: Name: QI JUN WAN; Phone Number: +8613537857368; Email: yiyuan2224@sina.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Second People's Hospital
      • Contact: Yi Xu; Phone Number: +8613798309505; Email: xuyi20001234@163.com
      • Contact: QiJun Wan; Phone Number: +8613537857368; Email: yiyuan2224@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacubitril/Valsartan treatment group; 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.	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.
Active Comparator: RAS inhibitor treatment group; 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
NT-proBNP	the change from baseline to 12 months in the NT-proBNP	12 months
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

Collaborators and Investigators

• Sponsor: Shenzhen Second People's Hospital
• Investigators: Principal Investigator: YI XU, Shenzhen Second People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2020
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 3, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Hemodialysis; Peritoneal dialysis; Cardiovascular Events; Sacubitril/valsartan; Efficacy Prediction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: 20200601054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No