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

NCT03636932 | Completed Phase 2

• 2 other identifiers: 2017-712018-003232-80
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

N-acetylcysteine (NAC) group

ACTIVE COMPARATOR

Drug: N-acetylcysteine (NAC); Biological: Blood sample

Placebo group

PLACEBO COMPARATOR

Drug: Placebo; Biological: Blood sample

Interventions

N-acetylcysteine (NAC) DRUG

Intravenous injection of 2 gram of N-acetylcysteine (NAC) during 4 weeks, 3 times per week during the first three hours of dialysis.

N-acetylcysteine (NAC) group

Placebo DRUG

Intravenous injection of 2 gram of Placebo during 4 weeks, 3 times per week during the first three hours of dialysis.

Placebo group

Blood sample BIOLOGICAL

Circulating tissue factor assay

N-acetylcysteine (NAC) group; Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hôpitaux de Marseille

Marseille, 13354, France

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Acetylcysteine; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jean-Olivier ARNAUD, Director

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2018
• First Posted: August 17, 2018
• Study Start: April 30, 2019
• Primary Completion: February 4, 2021
• Study Completion: May 23, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)