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Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula

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ClinicalTrials.gov Identifier: NCT01863914
Recruitment Status : Completed
First Posted : May 29, 2013
Last Update Posted : February 19, 2019
Sponsor:
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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 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
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : January 31, 2019

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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 ClinicalTrials.gov identifier (NCT number): NCT01863914


Locations
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Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan, 704
Sponsors and Collaborators
National Cheng-Kung University Hospital
Investigators
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Principal Investigator: Jun-Neng Roan, MD, PhD National Cheng-Kung University Hospital
Publications:
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Responsible Party: Lam Chen Fuh, Associate Professor, National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier: NCT01863914    
Other Study ID Numbers: 101-2314-B-006-045
First Posted: May 29, 2013    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The Ethical committee in National Cheng Kung University Hospital approved major modification of a reduction of case collection from 80 to 60 cases on 2018-8-9. The study had recruited a total of 60 cases in the trial before 2018-12-31. The results were under analysis by the statistician. Moreover, exposure of the treatment group and placebo group were not performed until after completion of data analysis by the statistician in early February. The results might be revealed as appropriate in the website.
Keywords provided by Lam Chen Fuh, National Cheng-Kung University Hospital:
ESRD
Diabetes mellitus
Endothelial progenitor cells
Hemodialysis
rosuvastatin
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Arteriovenous Fistula
Diabetes Mellitus
Fistula
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
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors