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

NCT04572724 | Unknown Phase 4

• 1 other identifier: 20200601054
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Peritoneal Dialysis Complication; Hemodialysis Complication; Heart Failure

Keywords

Sacubitril/valsartan; Peritoneal dialysis; Hemodialysis; Cardiovascular Events; Efficacy Prediction

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• change rate of cardiovascular events

  at least 18 months

• NT-proBNP

  12 months

• Kansas City Cardiomyopathy Questionnaire (KCCQ)

  1month, 6month,18 months

Study Arms (2)

Sacubitril/Valsartan treatment group

EXPERIMENTAL

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

RAS inhibitor treatment group

ACTIVE COMPARATOR

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

Interventions

Sacubitril / Valsartan Oral Tablet DRUG

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.

Sacubitril/Valsartan treatment group

RAS Inhibitors DRUG

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.

RAS inhibitor treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shenzhen Second People's Hospital: lead

Study Sites (1)

Shenzhen Second People's Hospital

Shenzhen, Guangdong, 518000, China

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• YI XU

  Shenzhen Second People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

YI XU

CONTACT

+8613798309505; xuyi20001234@163.com

QI JUN WAN

CONTACT

+8613537857368; yiyuan2224@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: it is a open label cohort study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The participants who met the inclusion and exclusion criteria will enrolled in the trial. 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 RAS inhibitor group.

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 1, 2020
• Study Start: July 6, 2020
• Primary Completion: November 1, 2022
• Study Completion: June 1, 2023
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)