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

Early Phase 1

• Conditions: CKD
• Interventions: Drug: LCZ 696

• Registration Number: NCT03771729
• Lead Sponsor: The Second Affiliated Hospital of Harbin Medical University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-11-30
• Status Verified: 2018-12
• Study First Submitted QC: 2018-12-09
• Last Update Submitted: 2018-12-09
• Study First Posted: 2018-12-11
• Last Update Posted: 2018-12-11
• Study Start: 2018-12-30
• Primary Completion: 2019-05-28
• Study Completion: 2019-06-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LCZ696 treatment	LCZ 696	LCZ696 200mg twice daily

Primary Outcome Measures

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

Secondary Outcome Measures

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