RENACTIF: Reduction of the Thrombotic Phenotype in Renal Insufficiency With N-AcetylCysteine
Status:
Unknown status
Trial end date:
2021-05-01
Target enrollment:
Participant gender:
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.