NCT03636932

RENACTIF: Reduction of the Thrombotic Phenotype in Renal Insufficiency With N-AcetylCysteine

RENACTIF: Reduction of the Thrombotic Phenotype in Renal Insufficiency With N-AcetylCysteine A Randomized, Double-blind, Placebo-controlled, Cross-over Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Assistance Publique Hopitaux De Marseille · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Chronic Kidney Disease (CKD) is a known risk factor of cardiovascular morbidity and mortality. In CKD, decline of renal function results in the accumulation of uremic toxins in blood and tissue, such as Indoxyl Sulfate (IS). IS plasma level is predictive of mortality and cardiovascular disease (CVD). Patients with CKD have increased oxidative stress and circulating tissue factor (TF) levels. In vitro, IS induces an inflammatory, pro-oxidative and pro-coagulant phenotype on endothelial cells and activates TF. N-acetylcysteine (NAC) protects endothelial cells from the effects of IS. NAC reduces oxidative stress and production of activated TF. A prospective study evaluating an oral NAC treatment versus placebo in chronic hemodialysis patients showed a better cardiovascular outcome but the physiopathology was unclear. The hypothesis is that NAC reduces cardiovascular risk by its effect on uremic toxin-induced pro-coagulant TF production. The primary objective is to compare the effect of NAC intravenously administered at each dialysis session (2gram on 3 dialysis sessions per week) to placebo on circulating TF levels in patients with CKD on chronic hemodialysis after 4 weeks of treatment. The objective is to show a 33% decrease in circulating tissue factor (TF) levels in the NAC group compared to the control group. It is a randomized, double-blind, placebo-controlled crossover trial that includes chronic hemodialysis patients from La Conception Hospital (AP-HM) in Marseilles, France. This is an interventional biomedical research project. 20 patients will be included in each group and will receive during 4 weeks intravenous injection. This study will give a pathophysiological rationale for the use of NAC to reduce thrombotic and cardiovascular risk in patients with CKD. This step will provide the rationale for a clinical trial to reduce the occurrence of major cardiovascular events with IV NAC in hemodialysis (HD) patients.

Conditions

• Chronic Kidney Diseases

Interventions

Type	Name	Description
DRUG	N-acetylcysteine (NAC)	Intravenous injection of 2 gram of N-acetylcysteine (NAC) during 4 weeks, 3 times per week during the first three hours of dialysis.
DRUG	Placebo	Intravenous injection of 2 gram of Placebo during 4 weeks, 3 times per week during the first three hours of dialysis.
BIOLOGICAL	Blood sample	Circulating tissue factor assay
BIOLOGICAL	Blood sample	The test of pro-coagulant activity of the tissue factor

Timeline

• Start date: 2019-04-30
• Primary completion: 2021-02-04
• Completion: 2023-05-23
• First posted: 2018-08-17
• Last updated: 2023-05-24

Locations

1 site across 1 country: France