Clinical Trial: Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effect of Rosuvastatin in the Mobilization of Endothelial Progenitor Cells and Graft Vascular Function Following Creation of Arteriovenous Fistula in Diabetic Patients Wit

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.

Detailed Summary:

Background In Taiwan, diabetic nephropathy is the second most common cause of end-stage renal disease (ESRD), but diabetic patients engender 12% more expense for care of dialysis than non-diabetic patients. ESRD patients with diabetes are also more frequently hospitalized due to problems such as failure of vascular access. Hemodialysis necessitates the placement of an arteriovenous (AV) fistula, which involves a direct anastomosis of the radial/brachial artery and cephalic vein. In the United States, procedures for creating the AV fistula and treatment of the related complication account for over 20% of hospitalizations of dialysis patients and cost about US$100 million annually. Two major hurdles in establishing a useable and patent AV fistula for dialysis are primary failure (failure of fistula to mature adequately for dialysis) and long-term survival of the vascular access. The reported primary failure rate varies from 20 to 50%. It has been shown that reduction of blood flow (>15% drop of flow over time) is the most critical factor for premature failure of AV fistula. Although blood flow in the venous site of AV fistula is also determined by the surrounding draining veins, blood pumped from the arterial site is the most important factor in maintaining sufficient fistula blood flow. However, very limited of studies have reported the effect of arterial blood flow on the function and patency of AV fistula. More evidences have shown that progressive failure of AV fistula after long-term use is due to the development of thrombosis (~80%) and stenosis (~20%). The mechanisms that underlie the failure of AV fistula are still poorly understood and there are very few, if any, specific therapeutic approaches that can increase the lifespan of these fistulas. Therefore, there is the critical need for experimental studies that seek to understand the basic mechanisms of primary failure and progressive failure of the AV fistula i
Sponsor: National Cheng-Kung University Hospital

Current Primary Outcome: Primary patent rate of AV fistula [ Time Frame: 6 months after operation ]

Original Primary Outcome: Primary patent rate of AV fistula [ Time Frame: 3 months after operation ]

Current Secondary Outcome: Composite outcome measurement of the overall shunt-related complication rate [ Time Frame: 6 months after operation ]

Original Secondary Outcome: Composite outcome measurement of the overall shunt-related complication rate [ Time Frame: 3 months after operation ]

Dates:
Date Received: February 14, 2013
Date Started: November 2012
Date Completion: December 2018
Last Updated: September 24, 2016
Last Verified: September 2016