Randomized Comparative Efficacy and Safety Study of Intermittent Simvastatin and Fenofibrate in Hemodialysis

Comparative Study of Effects and Safety of Intermittent Low Dose Therapy of Fenofibrate and Simvastatin on Chronic Hemodialysis Patients

Sixty chronic hemodialysis patients were randomly assigned to receive fenofibrate 100 mg (group 1, n = 30) or simvastatin 20 mg (group 2, n = 30) three times/week after their dialysis session. The safety and efficacy of drugs on lipid profile, oxidized low density lipoproteins (ox-LDL), glutathione peroxidase (GSH-Px) and C-reactive protein (CRP) were compared before and after 16-week treatment.

Study Overview

• Status: Completed
• Conditions: Fenofibrate/Simvastatin Comparison
• Intervention / Treatment: Drug: Fenofibrate; Drug: Simvastatin

Detailed Description

This is a prospective randomized open label parallel study.

The selected patients will be randomly allocated to one of two groups

• Group I (30 patients): Patients receiving fenofibrate (100 mg) taken on dialysis days after the dialysis session (three times per week).
• Group II (30 patients): Patients receiving simvastatin (20 mg) taken on dialysis days after the dialysis session (3 times per week).

A careful history of all patients including demographic characteristics, physical examination, chief complaint, past medical history, drug history, familial history, social history, disease(s).

Monitoring Parameters:

For efficacy, the following parameters are measured:

1. Lipid profile (total cholesterol, HDL, TG and LDL from Friedwald formula [10] {LDL-C= TC-[HDL + TG\5]). (measured at baseline and every month for 4 months)
2. C-reactive protein (CRP). (measured at baseline and after 4 months)
3. Oxidative stress markers: oxidized LDL and human glutathione peroxidase (measured at baseline and after 4 months).

For safety: (measured at baseline and every month for 4 months)

1. Observe for signs & symptoms of muscle toxicity and measure phosphocreatine kinase (CPK).
2. Liver function tests: ALT, AST, ALP & albumin.
3. Urea & serum creatinine. (to monitor renal function)
4. Hemoglobin
5. Other measurements: Body mass index (BMI), Blood Pressure, electrolytes (Sodium,potassium, calcium, phosphorous) and assess patient compliance by tablet counting.

Statistical analysis will be used to compare the effects of simvastatin and fenofibrate on lipid profile, inflammatory marker (CRP) and oxidative stress markers (oxidized LDL and glutathione peroxidase). In addition, comparing their safety on renal and hepatic functions, phosphocreatine kinase, blood pressure and blood glucose level.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Chronic hemodialysis patients with 3 dialysis sessions per week.

3. Lipid profile:

   1. Total Cholesterol ≥ 200 mg/dl or LDL ≥ 130 mg/dl.
   2. Triglycerides ≥ 150 mg/dl.

Exclusion Criteria:

1. Previous intolerance to fibrates or statins.
2. Use of any fibrates or statins within 6 months prior to study.
3. Hypothyroidism.
4. Active liver disease [unexplained persistent increase in liver enzymes (ALT & AST > 2x ULN)].
5. Uncontrolled hypertension.
6. History of MI or coronary bypass surgery in last 3 months.
7. Muscle toxicity (Phosphocreatine kinase (CPK) > 2x ULN).
8. Gall bladder disease.
9. Use of any immunosuppressant or steroid.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fenofibrate group; Group I (30 patients): Patients receiving fenofibrate (100 mg) taken on dialysis days after the dialysis session (three times per week).	Drug: Fenofibrate
Active Comparator: Simvastatin group; Group II (30 patients): Patients receiving simvastatin (20 mg) taken on dialysis days after the dialysis session (3 times per week).	Drug: Simvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C-reactive protein	16 weeks
oxidative stress markers (serum ox-LDL and GSH-Px)	16 weeks

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: August 31, 2016
• First Posted (Estimate): September 1, 2016

Study Record Updates

• Last Update Posted (Estimate): September 5, 2016
• Last Update Submitted That Met QC Criteria: September 1, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Dyslipidemia; Statins; Hemodialysis; Egypt; Fibrates; Improved Oxidative Stress
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Fenofibrate
• Other Study ID Numbers: CL (746)