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

Chronic Kidney Diseases Clinical Trial

— RENACTIF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03636932
• Other study ID #: 2017-71
• Secondary ID: 2018-003232-80
• Status: Completed
• Phase: Phase 2
• Start date: April 30, 2019
• Est. completion date: May 23, 2023

Study information

• Verified date: May 2023
• Source: Assistance Publique Hopitaux De Marseille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 23, 2023
• Est. primary completion date: February 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

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.
• 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
• Blood sample
The test of pro-coagulant activity of the tissue factor

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	compare the effect of N-acetylcysteine (NAC) intravenously administered	show a 33% decrease in circulating tissue factor levels in the N-acetylcysteine (NAC) group	12 months