Lipid-lowering Therapies in Vietnamese Chronic Kidney Disease Population

Phase 4

• Conditions: Hypercholesterolemia; Chronic Kidney Diseases
• Interventions: Drug: Ezetimibe/simvastatin 10/20 mg/day; Drug: Ezetimibe/simvastatin 10/40 mg/day; Drug: Simvastatin 40mg

• Registration Number: NCT03543774
• Lead Sponsor: Hue University of Medicine and Pharmacy

Brief Summary

This study aims to determine the mechanisms underlying dyslipidemia in chronic kidney disease (CKD) and effect of lipid-lowering therapies in patients with CKD via parameters of lipid, oxidative stress, tryptophan delegation as well as renal function and side effects. Thirty 3,4 CKD patients with low-density lipoprotein (LDL) \> 100 mg/mL (2,59mmol/l), randomly receive three different LDL lipid-lowering therapies: Simvastatin (40 mg/day) or ezetimibe/simvastatin combination (10/20 mg/day or 10/40 mg/day).

Detailed Description

The prevalence of chronic kidney disease (CKD) in Vietnamese population is increasing along with hypertension and diabetes. In CKD patient, cardiovascular disease (CVD) is the leading cause of mortality. The lipidemic disorder is one of the CV risk factors in CKD but it was not fully concerned in Viet Nam.

Hypocholesterolemia therapy has shown many benefits; however, its effects on OS and endothelial function are still not fully evidenced.

In clinical practice, physicians always concern the effects and safety before giving the prescription. However, despite the high frequency of statin treatment, only 1/3 of CKD patients achieved the LDL-C goal. Whether high-dose of statins mono-therapy is more effective in LDL-C lowering is still unclear, but are associated with a high rate of hepatotoxicity, myopathy.

Lowering LDL-C with statin mono-therapy and statin/ezetimibe combination reduces the risk of CVD in population without kidney disease. Which Cholesterol-lowering therapies are suitable for stage 3,4 CKD patients in term of e-GFR reduction and side effects? There is no data related to this field in the Vietnamese CKD population.

Thus, more advanced lipid-lowering therapies and a better understanding of the mechanism is needed for treatment strategy of hyperlipidemia in Vietnamese patients with CKD.

Study Timeline

• Study First Submitted: 2018-04-17
• Study First Submitted QC: 2018-05-18
• Study First Posted: 2018-06-01
• Study Start: 2018-06-15
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-13
• Primary Completion: 2020-03-15
• Study Completion: 2020-10-15

Recruitment & Eligibility

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

Inclusion Criteria

• Ages Eligible for Study:

  • ≥ 50 years old but not treated with chronic dialysis or kidney transplantation
  • In adults aged 18-49 years with CKD but not treated with chronic dialysis or kidney transplantation, statin treatment in people with one or more of the following: known coronary disease (myocardial infarction or coronary revascularization); diabetes mellitus; prior ischemic stroke; estimated 10-year incidence of coronary death or non-fatal myocardial infarction > 10%.

• CKD in the 3,4 stage: (e-GFR: 15-60 ml/min/1.73 m2)

• CKD proteinuria (defined as Creatinine clearance >20 ml/min/1.73 m2 combines with urinary protein excretion rate >300mg/24 h)

• LDL cholesterol concentration > 100 mg/dl (2,59 mmol/l)

Exclusion Criteria

In adults with dialysis-dependent CKD

• Heart failure (New York Heart Association class III or more)
• Previous or concomitant treatment with corticoids, statin, immunosuppressive agents, vitamin B6, B12, folate.
• Pregnancy
• Patients who do not agree to participate the research
• Patients are unable to understand the purposes and the risks of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EZE/simvastatin 10/20 mg treatment	Ezetimibe/simvastatin 10/20 mg/day	-
EZE/simvastatin 10/40 mg treatment	Ezetimibe/simvastatin 10/40 mg/day	-
simvastatin treatment	Simvastatin 40mg	-

Primary Outcome Measures

Name	Time	Method
To measure the serum level of Taurine, Tryp, and Kyn in Vietnamese CKD population and in healthy persons at the base time.	At the base time	The serum level of Taurine, Tryp, and Kyn will be measured in micromol/L
To measure the serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin in Vietnamese CKD population and in healthy persons at the base time.	At the base time	The serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin will be measured in mg/dL.
To measure the number of red blood cell, white blood cell and platelet in Vietnamese CKD population and in healthy persons at the base time.	At the base time	The number of red blood cell, white blood cell, and platelet will be measured in number/L
To measure the serum level of SGOT, SGPT, and Creatinin Kinase in Vietnamese CKD population and in healthy persons at the base time.	At the base time	The serum level of SGOT, SGPT and Creatinin Kinase will be measured in Units/L
To measure the level of Albuminuria and urine Creatinine in Vietnamese CKD population and in healthy persons at the base time.	At the base time	The serum level of Albuminuria and urine Creatinine will be measured in mg/dL
To measure the serum level of MDA in Vietnamese CKD population and in healthy persons at the base time.	At the base time	The serum level of MDA will be measured in nmol/L

Secondary Outcome Measures

Name	Time	Method
To measure the serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin in Vietnamese CKD population at 4th, 8th, 12th month.	at 4th, 8th and 12th month	The serum level of TC, LDL-C, HDL-C, TG, Creatinine, uric acid, and allantoin will be measured in mg/dL.; The change of results during treatment will be described and will be compared in 3 different groups
To measure the number of red blood cell, white blood cell and platelet in Vietnamese CKD population at 4th, 8th, 12th month.	at 4th, 8th and 12th month	The number of red blood cell, white blood cell, and platelet will be measured in number/L.; The change of results during treatment will be described and will be compared in 3 different groups
To measure the level of Albuminuria and urine Creatinine in Vietnamese CKD population at 4th, 8th, 12th month.	at 4th, 8th and 12th month	The level of Albuminuria and urine Creatinine will be measured in mg/dL. The change of results during treatment will be described and will be compared in 3 different groups
To measure the serum level of Taurine, Tryp, and Kyn in Vietnamese CKD population at 4th, 8th, 12th month.	at 4th, 8th and 12th month	The level of Taurine, Tryp, and Kyn will be measured in micromol/L. The change of results during treatment will be described and will be compared in 3 different groups
To measure the serum level of MDA in Vietnamese CKD population at 4th, 8th, 12th month.	at 4th, 8th and 12th month	The serum level of MDA will be serum in nmol/L. The change of results during treatment will be described and will be compared in 3 different groups
To measure the serum levels of SGOT, SGPT and Creatinine Kinase in Vietnamese CKD population at 4th month, 8th month and the 12th month	at 4th, 8th and 12th month	The unexpected effects of each treatment therapy on the liver and on the muscle will be accessed by measuring the level of SGOT, SGPT and Creatinine Kinase. These laboratory test will be measured at 4th month, 8th month and the 12th month. These results will be compared in 3 different groups

Trial Locations

Locations (1)

Hue University of Medicine and Pharmacy; 🇻🇳 Hue, Thua Thien Hue, Vietnam