The Effects of Lowering Low-density Lipoprotein Cholesterol Levels to New Targets on Cardiovascular Complications in Peritoneal Dialysis Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2009 by Clinical Research Center for End Stage Renal Disease, Korea
Sponsor:
Collaborator:
Ministry of Health & Welfare, Korea
Information provided by:
Clinical Research Center for End Stage Renal Disease, Korea
ClinicalTrials.gov Identifier:
NCT00999453
First received: October 18, 2009
Last updated: January 18, 2011
Last verified: October 2009
  Purpose

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in dialysis patients. Although significant improvements have been made in the management of CVD in the general population, it is not known whether these interventions would result in similar benefits in end stage renal disease patients.

Clinical studies conducted in the general population and in patients with established cardiovascular disease have found a strong independent association between lipid lowering, primarily LDL-cholesterol, and the risk of all-cause and cardiovascular mortality.

Therefore the National Cholesterol Education Panel (NCEP) has provided guidelines to lower LDL cholesterol levels to a goal of ≤100 mg/dl in patients with major risk factors of coronary heart disease. Moreover, the recent Adult Treatment Panel III (ATP III) guidelines provide an option to lower LDL cholesterol levels to a goal of <70 mg/dl in patients with very high risks for coronary heart disease.

The National Kidney Foundation K/DOQI guideline regards dialysis patients as having high risks for coronary heart disease and consequently recommends the LDL cholesterol level to be maintained under 100 mg/dl. This recommendation is in parallel to the NCEP ATP III guideline which has been proposed for the general population. However, data regarding cholesterol levels in dialysis patients have been conflicting, with some observational studies demonstrating and some not demonstrating a clear, relationship between LDL and cardiovascular end-points. In addition few randomized studies have been conducted in CKD patients.

An observational retrospective analysis of patients receiving hemodialysis, the U.S. Renal Data System Morbidity and Mortality Study, showed that the risk for cardiovascular mortality was decreased by 36 percent among patients receiving statins, compared to those who did not. Whereas, a most recent large prospective study in diabetic hemodialysis patients failed to demonstrate a significant reduction in cardiovascular endpoints with statin therapy.

Moreover, although HD and PD patients both develop chronic hypervolemia and inflammation as common findings, the relationship between risk factors and outcome may differ between these two treatment methods. The likely role of glucose from the dialysate in causing dyslipidemia in PD patients inherits a different strength of association between cholesterol level and outcome in HD and PD patients.

Therefore, this study aims to examine the clinical outcomes of treating chronic peritoneal dialysis patients with dyslipidemia to lower cholesterol levels, randomly assigning patients to either aggressive targets of LDL cholesterol of 70 mg/dl or current standard targets of LDLD cholesterol of 100 mg/dl.


Condition Intervention
Hypercholesterolemia
Other: LDL-cholesterol

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Clinical Research Center for End Stage Renal Disease, Korea:

Primary Outcome Measures:
  • Cardiovascular complication including acute coronary syndrome, cerebrovascular infarction and cardiovascular death [ Time Frame: 5 years (after detecting Cardiovascular complication) ] [ Designated as safety issue: No ]

Estimated Enrollment: 1222
Study Start Date: October 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDL-cholesterol 70 mg/dL or lower
'Experimental arm' is defined as patients treated to lower the level of low-density lipoprotein to 70 mg/dl or lower. 'Control arm' is defined as patients treated to lower low-density lipoprotein to a level of 100 mg/dl or lower.
Other: LDL-cholesterol
This is a 2-arm, open label, multi-center, randomized trial comparing aggressive to standard treatment of LDL-cholesterol. After screening, randomization, participants will be seen every 3 months during the follow-up period. An LDL-cholesterol 100 mg/dL is the goal for the standard group and the target for the aggressive group is 70 mg/dL. A lipid lowering algorithm has been developed based on the NCEP-ATP III recommendation which is used as a general guideline, allowing alterations based on the individual participants needs.
Active Comparator: LDL-cholesterol 100 mg/dL or lower
'Experimental arm' is defined as patients treated to lower the level of low-density lipoprotein to 70 mg/dl or lower. 'Control arm' is defined as patients treated to lower low-density lipoprotein to a level of 100 mg/dl or lower.
Other: LDL-cholesterol
This is a 2-arm, open label, multi-center, randomized trial comparing aggressive to standard treatment of LDL-cholesterol. After screening, randomization, participants will be seen every 3 months during the follow-up period. An LDL-cholesterol 100 mg/dL is the goal for the standard group and the target for the aggressive group is 70 mg/dL. A lipid lowering algorithm has been developed based on the NCEP-ATP III recommendation which is used as a general guideline, allowing alterations based on the individual participants needs.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. End-stage renal disease patients treated with peritoneal dialysis for 3 or more months
  2. LDL cholesterol 100 mg/dl or higher within 3 months and total cholesterol level 220 mg/dl or higher

Exclusion criteria:

  1. Hypersensitivity to statin, ezetimibe, fenofibrate
  2. Acute MI, angina, cerebrovascular accident, vascular intervention within the last 6 months
  3. Chronic obstructive pulmonary disease
  4. alanine transaminase > 3 times the upper normal limit
  5. creatine kinase > 3 times the upper normal limit
  6. Patients suffering form non-cardiac diseases with estimated survival less than 2 years
  7. Inevitable of cyclosporin, warfarin use
  8. Currently pregnant or breast feeding
  9. Any condition that might limit long-term compliance (e.g., psychiatric disorders)
  10. Participation in another clinical trial within 30 days prior to enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999453

Contacts
Contact: Shin-Wook Kang, M.D., PhD +82-2-2228-5345 kswkidney@yuhs.ac

Locations
Korea, Republic of
Recruiting
Kyungpook National University Hospital, Daegu, Korea, Republic of
Contact: Yong-Lim Kim, M.D.    +82-53-420-6305    ylkim@knu.ac.kr   
Contact: Ji-Young Choi, M.D.    +82-53-420-6311    jyss1002@hanmail.net   
Severance Hospital Recruiting
Seoul, Korea, Republic of
Contact: Shin-Wook Kang, M.D., PhD.    +82-2-2228-5345    kswkidney@yuhs.ac   
Sponsors and Collaborators
Clinical Research Center for End Stage Renal Disease, Korea
Ministry of Health & Welfare, Korea
Investigators
Principal Investigator: Shin-Wook Kang, M.D., PhD. professor of division of Nephrology, Severance Hospital, Korea
  More Information

No publications provided

Responsible Party: Shin-Wook Kang, Yonsei University College of Medicine
ClinicalTrials.gov Identifier: NCT00999453     History of Changes
Other Study ID Numbers: A-02
Study First Received: October 18, 2009
Last Updated: January 18, 2011
Health Authority: Korea: Food and Drug Administration

Keywords provided by Clinical Research Center for End Stage Renal Disease, Korea:
LDL-cholesterol
Prevalent peritoneal dialysis patients with hypercholesterolemia

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 24, 2014