Atorvastatin Treatment to Attenuate the Progression of Cardiovascular Disease in Hemodialysis Patients

Phase 3

Completed

• Conditions: Vascular Calcification; Atherosclerosis; Dyslipidemia; Inflammation
• Interventions: Drug: atorvastatin; Drug: placebo

• Registration Number: NCT00481364
• Lead Sponsor: Ercan OK

Brief Summary

This prospective, randomized, controlled study aims to investigate the effects of atorvastatin treatment in hemodialysis patients concerning progression of coronary artery calcification, progression of carotid artery intima-media thickness, endothelial function, and inflammation.

Detailed Description

The effects of statin treatment on coronary artery calcifications, carotid artery intima-media thickness, and endothelial functions have never been investigated in hemodialysis patients. Regarding inflammation, the present data in hemodialysis patients are derived from small studies with short follow-up.

We postulate that atorvastatin would reduce progression of coronary calcification and carotid artery intima-media thickness, decrease inflammation, and improve endothelial function.

In this prospective, controlled, randomized study, four hundred forty-six prevalent hemodialysis patients who meet inclusion and exclusion criteria will be randomized to atorvastatin (20 mg/day in first month; increased to 40 mg/day afterwards) and placebo arms (each arm consists of 223 patients), after completion of baseline investigations. Randomization will be performed with random permuted blocks and will be stratified according to dialysis center, age, sex, diabetic status, duration of dialysis, high flux dialyser use, and dialysate calcium level. Follow-up period will be twelve months.

It is estimated that 446 patients would provide 90% power with a two-sided, alpha error rate of 5%, of detecting a significant difference between treatment arms. Dropout rate is expected to be 20%, not to be replaced.

Study Timeline

• Study Start: 2006-11
• Study First Submitted: 2007-05-30
• Study First Submitted QC: 2007-05-30
• Study First Posted: 2007-06-01
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-06
• Last Update Posted: 2013-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 446

Inclusion Criteria

• aged between 18 and 80 years
• on maintenance bicarbonate hemodialysis scheduled thrice weekly, at least 12 hours/week
• willingness to participate to the study with a written informed consent

Exclusion Criteria

• to have serious life-limiting co-morbid situations, namely active malignancy, active infection, end-stage cardiac, pulmonary, or hepatic disease
• to be scheduled for living donor renal transplantation
• pregnancy or lactating
• history of coronary bypass grafting, acute myocardial infarction or unstable angina pectoris confirmed by angiography within three months of randomization
• presence of an absolute indication to use lipid lowering drug or an absolute contraindication for lipid lowering therapy according to investigator's opinion
• history of statin sensitivity or adverse reaction to statins
• receiving any lipid-lowering agents within three months of randomization
• uncontrolled hypothyroidism defined as TSH level higher than 1.5 times of upper limit
• receipt of any investigational drug within 30 days before randomization
• inability to tolerate oral medication or history of significant malabsorption
• treatment with steroids or immunosuppressive drugs
• alcohol abuse, drug abuse
• ALT and/or AST levels more than three times above the upper limit of normal or symptomatic hepatobiliary disease
• unexplained CK > 3 times the upper limit of the normal range
• inability to give informed consent because of mental incompetence or a psychiatric disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Statin	atorvastatin	Atorvastatin 40 mg/day
Placebo	placebo	placebo

Primary Outcome Measures

Name	Time	Method
progression of coronary artery calcification score	one year
progression of carotid artery intima-media thickness	one year
changes in the level of hsCRP	one year

Secondary Outcome Measures

Name	Time	Method
changes in the endothelial function	one year
changes in the level of hsCRP	one year

Trial Locations

Locations (1)

Ege University School of Medicine, Division of Nephrology; 🇹🇷 Bornova, Izmir, Turkey