NAC in Spontaneous Bacterial Peritonitis
Adjunctive N-Acetylcysteine in the Management of Spontaneous Bacterial Peritonitis in Patients With Liver Cirrhosis: A Randomized Controlled Trial
Spontaneous bacterial peritonitis (SBP) is one of the most serious infectious complications of liver cirrhosis and ascites. It affects approximately 10-30% of hospitalized patients with decompensated cirrhosis and carries an in-hospital mortality of 20-40% despite appropriate antimicrobial therapy (1,2). SBP results from bacterial translocation across the intestinal mucosa together with cirrhosis-associated immune dysfunction, leading to impaired bacterial clearance and exaggerated systemic inflammation (3). Current international guidelines recommend immediate empirical antibiotic therapy together with intravenous human albumin to reduce the incidence of acute kidney injury (AKI), hepatorenal syndrome, and mortality (2,4).
Although this strategy has substantially improved outcomes, treatment failure, persistent infection, renal dysfunction, acute-on-chronic liver failure (ACLF), and early mortality remain common, indicating that currently available therapy does not adequately address all pathogenic mechanisms of SBP (2,4). Increasing evidence suggests that oxidative stress is a central contributor to the progression of bacterial infections in cirrhosis. Excessive production of reactive oxygen species aggravates hepatocellular injury, endothelial dysfunction, immune dysregulation, and renal impairment, thereby amplifying systemic inflammatory responses during SBP (5,6). Consequently, therapeutic strategies targeting oxidative stress may improve host defense while limiting organ injury.
N-acetylcysteine (NAC) is a precursor of glutathione and one of the most extensively studied antioxidant agents in clinical medicine. Besides restoring intracellular glutathione stores, NAC exerts anti-inflammatory, endothelial-protective, and immunomodulatory effects through inhibition of oxidative stress and pro-inflammatory cytokine production (5,7). On the other hand, experimental studies have further demonstrated that NAC can inhibit bacterial biofilm formation, enhance antibiotic penetration, and potentiate antimicrobial activity against several clinically important bacterial pathogens (8,9).
Despite these promising biological properties, the therapeutic role of NAC in active SBP has not been established. Previous data have primarily evaluated NAC for hepato- or renal protection in liver disease (10). While its potential role as an adjunctive antibacterial therapy during active SBP has not been investigated in adequately designed randomized controlled trials. Therefore, the present study will evaluate whether adjunctive NAC improves early treatment response and reduces subsequent organ dysfunction and short-term adverse outcomes.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria: Adult patients (≥18 years) with liver cirrhosis, confirmed by clinical, radiological, or histopathological findings, who are newly diagnosed with SBP based on an ascitic fluid polymorphonuclear (PMN) leukocyte count ≥250 cells/mm³ according to the American Association for the Study of Liver Diseases (AASLD) criteria (2). Eligible participants were required to have undergone diagnostic paracentesis for ascitic fluid analysis and to provide informed consent prior to enrollment.
Exclusion Criteria
- Secondary bacterial or fungal peritonitis.
- Recent abdominal surgery or requiring immediate surgical intervention.
- Known hypersensitivity to NAC.
- Pregnancy or lactation.
- Septic shock, established HRS-AKI requiring rescue therapy, or renal replacement therapy at enrollment.
- Advanced malignancy or terminal illness.
- Previous NAC administration during the current SBP episode.
- Inability to receive oral study medication.
- Participation in another interventional trial that may affect study outcomes.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: CONTROL
|
Standard-of-care SBP therapy + matching placebo twice daily for 7 days.
|
|
Active Comparator: NAC
|
Standard-of-care SBP therapy + NAC 600 mg orally twice daily for 7 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Percentage change in ascitic-fluid polymorphonuclear (PMN) count from baseline to 48 hours after initiation of treatment
Time Frame: 48 H
|
Primary Outcome: Percentage change in ascitic-fluid polymorphonuclear (PMN) count from baseline to 48 hours after initiation of treatment. % change = [(48-h PMN - baseline PMN) / baseline PMN] × 100 |
48 H
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- NAC&SBP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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