Observation on the Effect of Sacubitril/Valsartan in Advanced Chronic Kidney Disease（CKD）Patients With Heart Failure

This paper will mainly present the renal results from a clinical study aimed to observe the effect of sacubitril/valsartan in advanced chronic kedney disease patients with heart failure.All patients will receive LCZ696.The results will be compared before and after treatment.

Study Overview

• Status: Unknown
• Conditions: CKD
• Intervention / Treatment: Drug: LCZ 696

Detailed Description

On trial entry, patients will first receive LCZ696 50mg twice daily.According to the condition of disease and tolerance,the dose will be doubled every 2 weeks until the target maintenance dose 200mg twice daily is reached unless potassium or change in kidney function preclude a dose increase(reduction in dose will be permitted if the larger dose will not be tolerated, and temporary interruption will be permitted at any time if required for clinical reasons).The trial will be followed up for 12 weeks. Study visits will be scheduled at 2,4,6,8,10and12 weeks (and additional visits will be arranged where necessary to monitor participant safety).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients diagnosed with Chronic kidney disease (eGFR<60 ml/ min/1.73m²) and heart failure
2. documented history of heart failure with associated signs or symptoms
3. New York Heart Association (NYHA) classes II-IV
4. mean sitting systolic blood pressure (msSBP) ⩾140mmHg
5. good compliance

Exclusion Criteria:

1. isolated right heart failure owing to pulmonary disease, dyspnoea from non-cardiac causes, primary valvular or myocardial diseases, or coronary or cerebrovascular diseases needing revascularization within 3months of screening or during the trial
2. acute renal failure
3. systolic blood pressure lower than 100 mm Hg at screening (<95 mm Hg at the randomisation visit)
4. significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy(such as serum potassium>5.5 or <3.5mmol/L, serum sodium<130mmol/L or alanine aminotransferase or aspartate aminotransferase>2 times the upper limit of the normal range)
5. history of angioedema（drug-related or otherwise)
6. any medications that have potential for drug-drug interaction with LCZ696 will not be allowed during the study 7)pregnant female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LCZ696 treatment; LCZ696 200mg twice daily	Drug: LCZ 696; LCZ696 200mg twice daily; Other Names: sacubitril/valsartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate(eGFR)	Blood samples will be collected for analysis of glomerular filtration rate(eGFR) every 2weeks .	12 weeks
Change in urinary microalbumin/creatinine ratio(uACR)	Urine samples will be collected for analysis of urinary microalbumin/creatinine ratio(uACR) every 2weeks.	12 weeks
Concentration of N terminal pro B type natriuretic peptide(NT-prpBNP)	Blood samples will be collected for analysis of concentration of N terminal pro B type natriuretic peptide(NT-proBNP) every 2weeks.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood uric acid	Blood samples will be collected for analysis of uric acid every 2weeks.	12 weeks
Rate of HbA1c	Blood samples will be collected for analysis of HbA1c every 2weeks.	12weeks
Systolic and diastolic blood pressure	Systolic and diastolic blood pressure will be measured every 2weeks.	12 weeks
left ventricle eject fraction	Cardiac ultrasound will be measured every 2weeks.	12 weeks
Concentration of postassium	Blood samples will be collected for analysis of concentration of postassium every 2weeks.	12 weeks
Concentration of serum troponin	Blood samples will be collected for analysis of concentration of serum troponin every 2weeks.	12 weeks
Concentration of alanine aminotransferase or aspartate aminotransferase	Blood samples will be collected for analysis of concentration of alanine aminotransferase or aspartate aminotransferase every 2weeks.	12 weeks
Concentration of sodio	Urine samples will be collected for analysis of concentration of sodion every 2weeks.	12 weeks

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 30, 2018
• Primary Completion (ANTICIPATED): May 28, 2019
• Study Completion (ANTICIPATED): June 15, 2019

Study Registration Dates

• First Submitted: November 30, 2018
• First Submitted That Met QC Criteria: December 9, 2018
• First Posted (ACTUAL): December 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2018
• Last Update Submitted That Met QC Criteria: December 9, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Heart Failure; Sacubitril/Valsartan; Advanced CKD Patients
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Renal Insufficiency; Heart Failure; Kidney Diseases; Renal Insufficiency, Chronic; 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: 42411671-X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Clinical Study Report (CSR)

Drug and device information, study documents

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