Lipid-lowering Therapies in Vietnamese Chronic Kidney Disease Population (VietCKD)

Lipid-lowering Regimes Improve Oxidative Stress, Tryptophan Degradation in Hypercholesterolemia Chronic Kidney Disease Patients

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).

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Diseases; Hypercholesterolemia
• Intervention / Treatment: Drug: Simvastatin 40mg; Drug: Ezetimibe/simvastatin 10/20 mg/day; Drug: Ezetimibe/simvastatin 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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Vietnam
  • Thua Thien Hue
    • Hue, Thua Thien Hue, Vietnam, 0234
      • Recruiting
      • Hue University of Medicine and Pharmacy
      • Contact: Nguyen Thanh Thao; Phone Number: 84.234.3822873; Email: hcmp@huemed-univ.edu.vn
      • Contact: Nguyen Thanh Thao; Phone Number: 84.234.3822873; Email: thaonrad@gmail.com
      • Principal Investigator: Duong Thi Ngoc Lan, Master
      • Sub-Investigator: Le Van An, A/Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: simvastatin treatment	Drug: Simvastatin 40mg; Simvastatin mono-therapy at the dose of 40 mg/day for 12 months
SHAM_COMPARATOR: EZE/simvastatin 10/20 mg treatment	Drug: Ezetimibe/simvastatin 10/20 mg/day; Ezetimibe/simvastatin combined therapy at the dose of 10/20 mg/day for 12 months
SHAM_COMPARATOR: EZE/simvastatin 10/40 mg treatment	Drug: Ezetimibe/simvastatin 10/40 mg/day; Ezetimibe/simvastatin combined therapy at the dose of 10/40 mg/day for 12 months

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	at 4th, 8th and 12th month
To measure the serum level of Taurine, Tryp, and Kyn in Vietnamese CKD population at 4th, 8th, 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	at 4th, 8th and 12th month
To measure the number of red blood cell, white blood cell and platelet in Vietnamese CKD population at 4th, 8th, 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	at 4th, 8th and 12th month
To measure the serum level of MDA in Vietnamese CKD population at 4th, 8th, 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	at 4th, 8th and 12th month
To measure the serum levels of SGOT, SGPT and Creatinine Kinase in Vietnamese CKD population at 4th month, 8th month and the 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	at 4th, 8th and 12th month
To measure the level of Albuminuria and urine Creatinine in Vietnamese CKD population at 4th, 8th, 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	at 4th, 8th and 12th month

Collaborators and Investigators

• Sponsor: Hue University of Medicine and Pharmacy
• Collaborators: Università degli Studi di Sassari
• Investigators: Principal Investigator: Duong Thi Ngoc Lan, Master, Hue University of Medicine and Pharmacy

Publications and helpful links

Helpful Links

• A Trial of Pitavastatin Versus Rosuvastatin for Dyslipidemia in Chronic Kidney Disease
• Effects of lowering LDL cholesterol on progression of kidney disease
• Ezetimibe and simvastatin for the prevention of cardiovascular events in predialysis chronic kidney disease patients: a review
• The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.
• Impact of cholesterol lowering treatment on plasma kynurenine and tryptophan concentrations in chronic kidney disease: Relationship with oxidative stress improvement
• 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
• KDOQI US Commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2018
• Primary Completion (ANTICIPATED): March 15, 2020
• Study Completion (ANTICIPATED): October 15, 2020

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (ACTUAL): June 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; Chronic kidney disease; Lipid lowering therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Kidney Diseases; Renal Insufficiency, Chronic; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
• Other Study ID Numbers: HueUMP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes