Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01863914
Recruitment Status : Recruiting
First Posted : May 29, 2013
Last Update Posted : October 17, 2017
Information provided by (Responsible Party):
Lam Chen Fuh, National Cheng-Kung University Hospital

Brief Summary:

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 or disease Intervention/treatment Phase
End-stage Kidney Disease Diabetes Mellitus Arteriovenous Fistula Drug: Rosuvastatin Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : November 2012
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Primary patent rate of AV fistula [ Time Frame: 6 months after operation ]
    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 :
  1. Composite outcome measurement of the overall shunt-related complication rate [ Time Frame: 6 months after operation ]
    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:
  1. Composite outcome measurement of systemic pro-inflammatory response [ Time Frame: 6 months after operation ]
    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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): 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

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
First Posted: May 29, 2013    Key Record Dates
Last Update Posted: October 17, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The study is now still recruting new cases. This study included 50 cases so far and is followed under review by Institution Review Borad in National Cheng Kung University Hospital. Extension of the study period from Dec. 2016 to Dec. 2018 is expected according to the rectuiting rate to reach an estimated case number of 80 patients. Application of the extension to the IRB in National Cheng Kung University will be processed in October, 2016. Individual participant data will not be presented in public; only summarized data will be available once the study had been completed (target case number fulfilled).

Keywords provided by Lam Chen Fuh, National Cheng-Kung University Hospital:
Diabetes mellitus
Endothelial progenitor cells

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