Ascorbic Acid on Restenosis of Dysfunctional Hemodialysis Vascular Access

National Taiwan University Hospital Hsin-Chu Branch

Status and phase: Completed; Phase 2

Conditions: Hemodialysis Access Failure

Treatments: Drug: Normal saline; Drug: Ascorbic Acid 600 MG; Drug: Ascorbic Acid 300 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT03524846

99G002

Details and patient eligibility

About

To investigate the effect of ascorbic acid on angiographic restenosis after percutaneous transluminal angioplasty (PTA) for dysfunctional dialysis vascular access.

Full description

Vascular access dysfunction is the leading cause of treatment insufficiency or interruption among hemodialysis (HD) patients, and it is responsible for a large portion of the cost of any end-stage renal disease (ESRD) program. Intimal hyperplasia at the venous segment of vascular access is the characteristic lesion, which leads to dysfunction or failure of both arteriovenous fistulas (AVF) and prosthetic grafts (AVG). Although percutaneous transluminal angioplasty (PTA) is effective in treating these stenotic lesions, the effect seems not permanent and restenosis after PTA remains a major problem. A number of studies have examined the clinical, anatomical, and technical factors for restenosis, the causes of restenosis are still not fully understood.This highlights a possible role of non-traditional risk factors to explain the high restenosis rate at the venous segment of vascular access, which includes oxidative stress, inflammation, and endothelial dysfunction.

Ascorbic acid (vitamin C) is a potent antioxidant used for a long time. Hemodialysis patients had been shown to be deficient in antioxidant defense, which resulted in increasing requirement of ascorbic acid supplement. Currently, intravenous 300-mg ascorbic acid supplementation three times a week after hemodialysis had been used to overcome erythropoietin resistance in patients with iron deficiency. Theoretically, ascorbic acid scavenges reactive oxygen species and reactive nitrogen species and may thereby prevent oxidative injuries. Investigators reported that administration of high dose ascorbic acid could prevent lipid peroxidation and oxidative DNA damage in patients with ESRD.

In this study, the investigators investigated whether ascorbic acid could decrease venous restenosis after PTA for dysfunctional hemodialysis vascular access.

Enrollment: 93 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• clinical signs, i.e., decreased thrill, development of collateral veins, limb swelling, and prolonged bleeding from puncture sites, suggesting vascular access dysfunction
• reduction of flow rate more than 25% from baseline
• total access blood flow rate less than 500 mL/min by ultrasound dilution method
• increased venous pressure during dialysis, as dynamic venous pressure exceeding threshold levels of 150 mmHg in AVF and 160 mmHg in AVG, respectively, under dialysis blood flow 250 ml/min for three consecutive times

Exclusion criteria

• hospitalized for infection, heart failure, or acute coronary syndrome in recent 3 months
• unable to comply with follow-up visits
• already under ascorbic acid or other antioxidant supplements

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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93 participants in 3 patient groups, including a placebo group

Ascorbic acid 300 mg

Active Comparator group

Description:

Ascorbic acid 300 mg was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.

Treatment:

Drug: Ascorbic Acid 300 MG

Ascorbic acid 600 mg

Active Comparator group

Description:

Ascorbic acid 600 mg was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.

Treatment:

Drug: Ascorbic Acid 600 MG

Placebo

Placebo Comparator group

Description:

Normal saline was administered intravenously for 5 minutes after each dialysis session, three times per week for 12 weeks.

Treatment:

Drug: Normal saline