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

Primary Purpose

Peritoneal Dialysis Complication, Hemodialysis Complication, Heart Failure

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Sacubitril / Valsartan Oral Tablet
RAS Inhibitors
Sponsored by
Shenzhen Second People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peritoneal Dialysis Complication focused on measuring Sacubitril/valsartan, Peritoneal dialysis, Hemodialysis, Cardiovascular Events, Efficacy Prediction

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shenzhen Second People's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sacubitril/Valsartan treatment group

RAS inhibitor treatment group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

cardiovascular events
death from any kinds of cardiovascular diseases
hospitalization for heart failure
time from the day of enroll to a first unplanned hospitalization for heart failure

Secondary Outcome Measures

change rate of cardiovascular events
change rate of composite of death from cardiovascular diseases or a first unplanned hospitalization for heart failure
NT-proBNP
the change from baseline to 12 months in the NT-proBNP
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.

Full Information

First Posted
September 28, 2020
Last Updated
October 3, 2020
Sponsor
Shenzhen Second People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04572724
Brief Title
The Effect of Sacubitril/Valsartan on Cardiovascular Events in Dialysis Patients and Efficacy Prediction of Baseline LVEF Value
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 6, 2020 (Actual)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shenzhen Second People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peritoneal Dialysis Complication, Hemodialysis Complication, Heart Failure
Keywords
Sacubitril/valsartan, Peritoneal dialysis, Hemodialysis, Cardiovascular Events, Efficacy Prediction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
None (Open Label)
Masking Description
it is a open label cohort study
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sacubitril/Valsartan treatment group
Arm Type
Experimental
Arm Description
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.
Arm Title
RAS inhibitor treatment group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sacubitril / Valsartan Oral Tablet
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
RAS Inhibitors
Intervention Description
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.
Primary Outcome Measure Information:
Title
cardiovascular events
Description
death from any kinds of cardiovascular diseases
Time Frame
at least 18 months
Title
hospitalization for heart failure
Description
time from the day of enroll to a first unplanned hospitalization for heart failure
Time Frame
at least 18 months
Secondary Outcome Measure Information:
Title
change rate of cardiovascular events
Description
change rate of composite of death from cardiovascular diseases or a first unplanned hospitalization for heart failure
Time Frame
at least 18 months
Title
NT-proBNP
Description
the change from baseline to 12 months in the NT-proBNP
Time Frame
12 months
Title
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Description
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.
Time Frame
1month, 6month,18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
YI XU
Phone
+8613798309505
Email
xuyi20001234@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
QI JUN WAN
Phone
+8613537857368
Email
yiyuan2224@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YI XU
Organizational Affiliation
Shenzhen Second People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shenzhen Second People's Hospital
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
YI XU
Phone
+8613798309505
Email
xuyi20001234@163.com
First Name & Middle Initial & Last Name & Degree
QIJUN WAN
Phone
+8613537857368
Email
yiyuan2224@sina.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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