Effect of N-acetylcysteine as Adjunct Therapy on the Clinical Outcome of Neonatal Sepsis

Neonatal sepsis (NS) is a life-threatening condition characterized by systemic inflammation in response to infection during the first 28 days of life. Nowadays, it is generally acknowledged that one of the critical pathogenic mechanisms involved in neonatal sepsis is oxidative stress, which plays a critical role in amplifying inflammation and cellular injury. During sepsis, activated immune cells such as neutrophils and macrophages produce large amounts of ROS and RNS as part of the antimicrobial defense. Also, IL-6 and IL-8 are the main cytokines involved in the initiation of the sepsis cascade in the newborn, following that, several oxidative stress-related pathways are activated through different mechanisms, triggering the initiation of a self-maintaining "sepsis redox cycle" finally leading to cell oxidative damage and mitochondria dysfunction. One of the major consequences of oxidative stress is lipid peroxidation, in which ROS attack polyunsaturated fatty acids (PUFAs) in cellular membranes which leads to membrane dysfunction and cellular injury. One of the major consequences of oxidative stress is lipid peroxidation, in which ROS attack polyunsaturated fatty acids (PUFAs) in cellular membranes which leads to membrane dysfunction and cellular injury. Elevated levels of MDA in neonatal sepsis are associated with increased oxidative damage and worse clinical outcomes, making it a valuable marker for assessing the oxidative burden in sepsis. N-acetylcysteine (NAC) has the ability to replenish intracellular glutathione levels and neutralize ROS makes it promising as adjunct therapy in neonatal sepsis. administering NAC to neonates with sepsis could potentially improve clinical outcomes by reducing oxidative damage through replenishing glutathione and scavenging free radicals result in reduction of MDA level which is a biomarker for lipid peroxidation and oxidative damage, preserving organ function, and preventing the progression to severe complications like MODS. NAC efficacy in neonatal sepsis is not studied yet, and it is unknown whether NAC is beneficial as adjunct therapy for neonatal sepsis or not.

The aim of this study is to evaluate the efficacy of N-acetylcysteine as an adjunctive therapy in neonatal sepsis by assessing clinical improvement using the sepsis score and nSOFA score, reduction of oxidative stress through changes in malondialdehyde (MDA) levels, and its impact on the length of hospital stay and mortality.

Study Overview

• Status: Not yet recruiting
• Conditions: Neonatal Sepsis
• Intervention / Treatment: Drug: N-Acetyl Cysteine (NAC); Other: Normal Saline

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age at admission: Near-term and term (≥ 32 gestational weeks) neonates up to 28 days of life.
• Neonates diagnosed with sepsis: diagnosis of sepsis based on high probable sepsis (HPS) and probable sepsis (PRS) according to the criteria employed for defining the sepsis score.

Exclusion Criteria:

• Critical major congenital anomalies that are incompatible with first 28 days vitality.
• Hypersensitivity to NAC
• Parents or guardians who decline consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interventional Group; A group of 25 neonates who will receive (12.5 mg/kg for preterm and 25 mg/kg for full-term neonates) of NAC intravenously every 12 hours for 3 days. in addition to the standard neonatal sepsis care in the unit.	Drug: N-Acetyl Cysteine (NAC); A group of 25 neonates will receive (12.5 mg/kg for preterm and 25 mg/kg for full-term neonates) of NAC intravenously every 12 hours for 3 days. Each dose will be infused over 60 min
Placebo Comparator: Control Group; A group of 25 neonate controls will receive Normal saline in the same volume of the diluted NAC. In addition to the standard neonatal sepsis care in the unit.	Other: Normal Saline; A group of 25 neonates as controls will receive Normal saline in the same volume of the diluted NAC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Sepsis Classification Based on Predefined Clinical and Laboratory Criteria	Neonates will be classified into one of four categories: highly probable sepsis, probable sepsis, possible sepsis, or no sepsis, according to predefined clinical and laboratory criteria. Classification is based on: Number of sepsis-related clinical signs (including temperature instability, apnea, need for oxygen or ventilation, tachycardia or bradycardia, hypotension, feeding intolerance, abdominal distension, and necrotizing enterocolitis) C-reactive protein (CRP) level (cutoff 5 mg/mL) Presence of altered hematological parameters (white blood cell count, absolute neutrophil count, and platelet count) Blood culture results This outcome represents a categorical diagnostic classification, not a numerical scoring scale.	From enrollment to the end of treatment at 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Sequential Organ Failure Assessment (nSOFA) Score	The Neonatal Sequential Organ Failure Assessment (nSOFA) score ranges from 0 to 15, with higher scores indicating worse organ dysfunction. The nSOFA score will be recorded during the study period.	From enrollment to the end of treatment (3 days)
Malondialdehyde (MDA) levels.	Serum malondialdehyde (MDA) level will be measured as a biomarker of oxidative stress using a validated laboratory method and reported in nmol/mL.	From enrollment to the end of treatment at 3 days
Recording of Safety and Tolerability of NAC	Safety and tolerability will be assessed by monitoring adverse events related to N-acetylcysteine administration throughout the study period.	From day 1 to day 28.
Incidence of Multiple Organ Dysfunction Syndrome (MODS)	The occurrence of multiple organ dysfunction syndrome (MODS) will be recorded as a binary outcome (yes/no) during the study period.	From day 1 to day 28.
Length of Hospital Stay	Length of hospital stay will be calculated as the number of days from admission to hospital discharge.	From day 1 to day 28.
Recording of Mortality	Mortality will be assessed by recording the number of death cases in each study group during the neonatal period.	From day 1 to day 28.

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 20, 2025
• First Submitted That Met QC Criteria: January 24, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 24, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: NAC; MDA; Neonatal Sepsis; nSOFA; Sepsis Score
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Neonatal Sepsis; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Pharmaceutical Preparations; Amino Acids; Crystalloid Solutions; Isotonic Solutions; Solutions; Cysteine; Amino Acids, Sulfur; Acetylcysteine; Saline Solution
• Other Study ID Numbers: FMASU MS 661/2025

Drug and device information, study documents

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