Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by National Cheng-Kung University Hospital
Information provided by (Responsible Party):
Lam Chen Fuh, National Cheng-Kung University Hospital Identifier:
First received: February 14, 2013
Last updated: December 25, 2015
Last verified: December 2015

Background Arteriovenous (AV) fistula is the most common vascular access for long-term hemodialysis in the end-stage renal disease (ESRD) patients. About 25% of these patients are diabetes mellitus. However, the effects of hyperglycemia on the vascular function of arteriovenous fistula are still remained unclear. Studies have shown that blood flow in the AV fistula is significantly reduced in patients with diabetes mellitus. Diabetic patients also require a longer period of time for the maturation of AV fistula, and have slightly higher complication rate than non-diabetic patients. Statins have been widely shown to mediate several important pleiotropic effects in the improvement of vascular endothelial dysfunction, attenuation of inflammatory responses, stabilization of atherosclerotic plaques, inhibition of vascular smooth muscle proliferation, and modulation of procoagulant activity and platelet function.Our experimental studies in diabetic animals demonstrate that administration of a water-soluble statin rosuvastatin significantly improves the fistula flow, vascular function and luminal dilatation of AV fistula in diabetic rats by suppression of vascular oxidative stress and inflammatory load.

Study hypothesis The central hypothesis of this research project is rosuvastatin mediates pleiotropic protective effect on vascular endothelial function and suppresses the regional pro-inflammatory reaction in the vasculature, therefore administration of rosuvastatin during the perioperative period of creation of native AV fistulas in diabetic patients with ESRD may potentiate the vascular function and reduce the primary failure rate of AV fistulae.

Condition Intervention Phase
End-stage Kidney Disease
Diabetes Mellitus
Arteriovenous Fistula
Drug: Rosuvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Rosuvastatin in the Mobilization of Endothelial Progenitor Cells and Graft Vascular Function Following Creation of Arteriovenous Fistula in Diabetic Patients With Chronic Renal Failure

Resource links provided by NLM:

Further study details as provided by National Cheng-Kung University Hospital:

Primary Outcome Measures:
  • Primary patent rate of AV fistula [ Time Frame: 6 months after operation ] [ Designated as safety issue: No ]
    The definition of primary patency of an AV fistula is defined as successful cannulation of the fistula for first hemodialysis treatment (first dialysis session)(reference: BioMed Central Nephrology 2013;14:79). Administration of rosuvastatin protects the endothelial function in the AV fistula and restores the blood flow rate in the shunt of diabetic patients with ESRD, thereby improves the primary patent rate and early maturation of these fistulas

Secondary Outcome Measures:
  • Composite outcome measurement of the overall shunt-related complication rate [ Time Frame: 6 months after operation ] [ Designated as safety issue: No ]
    The most commonly shunt-related complications are formation of aneurysms, failure of shunt to mature, and development of thrombosis in AV fistula (Ann Vasc Surg 2012;26:680). The occurrence of shunt-related complications usually require surgical reintervention. Administration of rosuvastatin improves the vascular function of AV fistulas in diabetic patients with ESRD, therefore reduces the overall shunt-related complication rate and the requirement for surgical re-interventions.

Other Outcome Measures:
  • Composite outcome measurement of systemic pro-inflammatory response [ Time Frame: 6 months after operation ] [ Designated as safety issue: No ]
    Systemic proinflammatory response is determined by measuring blood concentrations of monocyte chemo-attractant protein (MCP)-1, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha, and the numbers of circulating endothelial progenitor cells (EPCs). Administration of rosuvastatin is associated with reduction of the systemic pro-inflammatory response and oxidative stress (levels of proinflammatory cytokines and other mediators in the circulation) in diabetic patients with ESRD. On the other hand, administration of rosuvastatin may mobilize the bone marrow-derived EPCs into systemic circulation, and the number of these circulating endothelial progenitors may provide prognostic value to the outcomes of AV fistula.

Estimated Enrollment: 80
Study Start Date: November 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo tablet contains only inactive ingredient. The placebo tablets will be taken once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)
Drug: Rosuvastatin
Arteriovenous fistula surgery was performed after 1-week treatment with placebo or Rosuvastatin (randomized, double blind). The intervention drug treatment continues for 3 more weeks after creation of AV fistula.
Other Name: Crestor
Active Comparator: Rosuvastatin
Rosuvastatin (CrestorÒ, Astrazeneca) 5mg once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)
Drug: Rosuvastatin
Arteriovenous fistula surgery was performed after 1-week treatment with placebo or Rosuvastatin (randomized, double blind). The intervention drug treatment continues for 3 more weeks after creation of AV fistula.
Other Name: Crestor

  Show Detailed Description


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Patients with diabetes mellitus (postprandial blood sugar >140 mg/dl)
  2. Patients with end-stage kidney disease and is proposed to undertake chronic hemodialysis
  3. Patients of age 18-65 years
  4. The fistula is constructed in the forearm (radiocephalic fistula).

Exclusion Criteria:

  1. Preoperative blood sugar level >250 mg/dl or most recent HbA1c >10%
  2. Recent treatment with statins within 2 weeks before evaluation for clinical trial
  3. Advanced liver disease
  4. Chronic alcoholism
  5. Congestive heart failure
  6. Coronary disease which require permanent statin therapy
  7. Malignancy or hematologic disorder
  8. Pregnancy or breastfeeding
  9. Past history of creation of AV fistula
  10. Scheduled for general anesthesia
  11. Emergent operation
  12. peripheral arterial occlusion disease
  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 identifier: NCT01863914

Contact: Jun-Neng Roan, MD 886-0928225368

National Cheng Kung University Hospital Recruiting
Tainan, Taiwan, 704
Contact: Chen-Fuh Lam, MD, PhD    8866-2353535 ext 5348   
Principal Investigator: Chen-Fuh Lam, MD, PhD         
Sub-Investigator: Jun-Neng Roan, MD         
Sponsors and Collaborators
National Cheng-Kung University Hospital
Principal Investigator: Jun-Neng Roan, MD National Cheng-Kung University Hospital
  More Information

Responsible Party: Lam Chen Fuh, Associate Professor, National Cheng-Kung University Hospital Identifier: NCT01863914     History of Changes
Other Study ID Numbers: 101-2314-B-006-045 
Study First Received: February 14, 2013
Last Updated: December 25, 2015
Health Authority: Taiwan: Institutional Review Board

Keywords provided by National Cheng-Kung University Hospital:
Diabetes mellitus
Endothelial progenitor cells
Blood flow

Additional relevant MeSH terms:
Arteriovenous Malformations
Arteriovenous Fistula
Diabetes Mellitus
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pathological Conditions, Anatomical
Renal Insufficiency
Urologic Diseases
Vascular Diseases
Vascular Fistula
Vascular Malformations
Rosuvastatin Calcium
Anticholesteremic Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 24, 2016