Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula

NCT01863914 | Completed Phase 2

• 1 other identifier: 101-2314-B-006-045
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

End-stage Kidney Disease; Diabetes Mellitus; Arteriovenous Fistula

Keywords

ESRD; Diabetes mellitus; Endothelial progenitor cells; Hemodialysis; rosuvastatin

Outcome Measures

Primary Outcomes (1)

• Primary patent rate of AV fistula

  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

  6 months after operation

Secondary Outcomes (1)

• Composite outcome measurement of the overall shunt-related complication rate

  6 months after operation

Other Outcomes (1)

• Composite outcome measurement of systemic pro-inflammatory response

  6 months after operation

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Rosuvastatin

ACTIVE COMPARATOR

Rosuvastatin (CrestorÒ, Astrazeneca) 5mg once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

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.

Also known as: Crestor

Placebo; Rosuvastatin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Preoperative blood sugar level \>250 mg/dl or most recent HbA1c \>10%
• Recent treatment with statins within 2 weeks before evaluation for clinical trial
• Advanced liver disease
• Chronic alcoholism
• Congestive heart failure
• Coronary disease which require permanent statin therapy
• Malignancy or hematologic disorder
• Pregnancy or breastfeeding
• Past history of creation of AV fistula
• Scheduled for general anesthesia
• Emergent operation
• peripheral arterial occlusion disease

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Study Sites (1)

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Related Publications (2)

• Roan JN, Fang SY, Chang SW, Hsu CH, Huang CC, Chiou MH, Tsai YC, Lam CF. Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model. J Vasc Surg. 2012 Nov;56(5):1381-9.e1. doi: 10.1016/j.jvs.2012.03.243. Epub 2012 Jun 22.

  PMID: 22727844 BACKGROUND

• Fang SY, Roan JN, Lin Y, Hsu CH, Chang SW, Huang CC, Tsai YC, Lam CF. Rosuvastatin suppresses the oxidative response in the venous limb of an arteriovenous fistula and enhances the fistula blood flow in diabetic rats. J Vasc Res. 2014;51(2):81-9. doi: 10.1159/000357619. Epub 2014 Jan 15.

  PMID: 24434545 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Diabetes Mellitus; Arteriovenous Fistula

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Arteriovenous Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Fistula; Vascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fistula; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jun-Neng Roan, MD, PhD

  National Cheng-Kung University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: May 29, 2013
• Study Start: November 1, 2012
• Primary Completion: December 31, 2018
• Study Completion: January 31, 2019
• Last Updated: February 19, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)