RENACTIF: Reduction of the Thrombotic Phenotype in Renal Insufficiency With N-AcetylCysteine A Randomized, Double-blind, Placebo-controlled, Cross-over Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- compare the effect of N-acetylcysteine (NAC) intravenously administered
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hemodialysis patients regardless of the etiology of their renal insufficiency for more than 3 months on a cycle of 3 sessions per week
- •Hemodialysis patients at least 4 hours per dialysis session
- •Patients with a weight of more than 40 kilogram
- •Patients capable of giving informed consent, agreeing to participate in the study and having signed a consent
- •Patient able to understand a written questionnaire
排除标准
- •Pregnant or lactating women
- •Persons deprived of their liberty or hospitalized without consent
- •Majors under legal protection or unable to express their consent
- •Possibility of recovery of renal function (scleroderma for example)
- •Chronic progressive infection that may affect their thrombotic risk
- •Patients under 40 kilogram
- •Patient taking oral anticoagulants
- •Patient with a known allergy to the active molecule or to any of its excipients
研究组 & 干预措施
Placebo group
干预措施: Placebo (Drug)
N-acetylcysteine (NAC) group
干预措施: N-acetylcysteine (NAC) (Drug)
N-acetylcysteine (NAC) group
干预措施: Blood sample (Biological)
Placebo group
干预措施: Blood sample (Biological)
结局指标
主要结局
compare the effect of N-acetylcysteine (NAC) intravenously administered
时间窗: 12 months
show a 33% decrease in circulating tissue factor levels in the N-acetylcysteine (NAC) group
次要结局
未报告次要终点