Clinical and Molecular Effects of N-Acetylcysteine Treatment in COVID-19-Related Acute Respiratory Distress Syndrome (A Prospective)

Clinical and Molecular Effects of N-Acetylcysteine Treatment in COVID-19-Related Acute Respiratory Distress Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

Prospective, randomized, double-blind, placebo-controlled clinical trial evaluating the clinical and molecular effects of intravenous N-acetylcysteine (NAC) in patients with COVID-19-associated acute respiratory distress syndrome (ARDS) treated in the intensive care unit. The study assessed inflammatory and thromboinflammatory biomarkers, hypoxia-related gene expression (HIF-1α, ACE2, CD147), and clinical outcomes including mortality and length of ICU stay.

Study Overview

• Status: Completed
• Conditions: COVID-19-Associated Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Diagnostic test: N-Acetylcysteine (NAC)

Detailed Description

This single-center, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted in adult patients with PCR-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) admitted to the intensive care unit. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous N-acetylcysteine (NAC) or placebo in addition to standard care. NAC was administered at a dose of 150 mg/kg on day 1 followed by 50 mg/kg/day on days 2 and 3.

The primary objectives were to evaluate the effects of NAC on inflammatory and thromboinflammatory biomarkers and hypoxia-related molecular pathways. Biochemical parameters including C-reactive protein, D-dimer, ferritin, zinc levels, and PaO₂/FiO₂ ratio were measured at ICU admission and on day 4. Gene expression levels of HIF-1α, ACE2, and CD147 were analyzed in peripheral blood using RT-qPCR.

Secondary objectives included assessment of clinical outcomes such as mortality, length of intensive care unit stay, and need for mechanical ventilation. The study was approved by the institutional ethics committee, and written informed consent was obtained from patients or their legal representatives.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Gaziantep, Turkey (Türkiye), 27
    • Gaziantep University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:Age ≥18 years

PCR-confirmed SARS-CoV-2 infection

Diagnosis of acute respiratory distress syndrome (ARDS) according to the Berlin criteria

Admission to the intensive care unit

Written informed consent obtained from the patient or legal representative -

Exclusion Criteria:Expected mortality within 48 hours of ICU admission

Prior chronic oxygen therapy

Previous COVID-19 treatment initiated at another center

Pregnancy or breastfeeding

Use of antioxidant or anti-inflammatory drugs within 30 days prior to enrollment

Known hypersensitivity to N-acetylcysteine

Use of medications affecting glutathione metabolism

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-Acetylcysteine (NAC) Group; Participants received intravenous N-acetylcysteine (150 mg/kg on day 1, followed by 50 mg/kg/day on days 2 and 3) in addition to standard of care.	Diagnostic test: N-Acetylcysteine (NAC); Intravenous N-acetylcysteine administered at 150 mg/kg on day 1 followed by 50 mg/kg/day on days 2 and 3, in addition to standard of care.; Other Names: NAC
Placebo Comparator: Plasebo; Participants received intravenous 0.9% sodium chloride (placebo) administered at the same volume and duration as the intervention group, in addition to standard of care.	Diagnostic test: N-Acetylcysteine (NAC); Intravenous N-acetylcysteine administered at 150 mg/kg on day 1 followed by 50 mg/kg/day on days 2 and 3, in addition to standard of care.; Other Names: NAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inflammatory and thromboinflammatory biomarkers	Change in C-reactive protein (CRP) and D-dimer levels from baseline (ICU admission) to day 4 of treatment.	Baseline (ICU admission) to Day 4

Collaborators and Investigators

• Sponsor: University of Gaziantep

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): June 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: January 21, 2026
• First Submitted That Met QC Criteria: January 21, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: TF.20.26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No