Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients

Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients: A Double-Blind Randomized Placebo-Controlled Trial

• Study the effect of acetylcysteine on decreasing the incidence of LIT in critically ill patients.
• Study the impact of acetylcysteine on the time to onset of LIT and the time to recovery of platelets.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Thrombocytopenia; Linezolid; ICU; Antioxidant
• Intervention / Treatment: Drug: N acetyl cysteine; Drug: Placebo

Detailed Description

Primary outcome: difference in incidence of LIT between patients who received NAC and patients who didn't.

• Primary outcome definition: Defined as platelets < 150000 OR decrease > 50% of baseline platelets.
• Secondary outcome: difference in Time to onset of LIT and time to recovery between the 2 groups. Blood products transfusion, bleeding, length of stay, and in-hospital mortality incidence between 2 groups.
• Secondary outcome definitions: after having thrombocytopenia, regardless of discontinuation of linezolid, recovery is defined as the restoration and maintenance of platelet counts > 70% of baseline values.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • 15 May hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients (age ≥ 18 years)
• Admitted to the Intensive Care Unit (ICU)
• Candidates for intravenous linezolid therapy for ≥ 48 hours

Exclusion Criteria:

• Baseline platelet count < 50 × 10⁹/L
• Diagnosis of malignancy
• Receipt of any chemotherapeutic agent within the past 6 months
• Positive COVID-19 RT-PCR test at admission
• Diagnosis of immune thrombocytopenia
• Presence of splenomegaly
• Presence of liver cirrhosis
• Presence of hepatitis C
• Refusal to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetylcysteine group; Generic name: N-acetylcysteine.; Trade name: Fluimucil.; Company: Zambon.; Dosage form: ampoules for intravenous administration.; Dose: 600mg taken every 12 hours daily with a fixed dose as there is no need for renal or hepatic adjustment, starting with the inception of linezolid therapy.; Duration: for 14 days post linezolid discontinuation or until ICU discharge, whichever came first.	Drug: N acetyl cysteine; Fluimucil 600 mg iv to be taken twice daily as infusion; Other Names: NAC; Fluimucil
Placebo Comparator: Standard of care; They will receive standard of care (Platelets monitoring daily, linezolid discontinuation if platelet count less than 50000 or clinically appropriate and platelet transfusion according to the institutional protocol) plus placebo (20 ml normal saline twice daily)	Drug: Placebo; 20 ml normal saline iv every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference in incidence of LIT between patients who received NAC and patients who didn't.	Defined as platelets < 150000 OR decrease > or = 50% of baseline platelets.	From starting linezolid untill 14 days after linezolid discontinuation or ICU discharge whichever comes first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood products transfusion, bleeding, length of ICU stay, and in-ICU mortality incidence between 2 groups.		From start linezolid until ICU discharge
Difference in time to platelet recovery between the 2 groups	after having thrombocytopenia, regardless of discontinuation of linezolid, recovery is defined as the restoration and maintenance of platelet counts > 70% of baseline values	From thrombocytopenia onset to recovery, assesed up to 14 days after linezolid discontinuation or ICU discharge whichever comes first
Difference in time to thrombocytopenia onset between the 2 groups		From linezolid start date until date of first thrombocytopenia event, assessed up to 14 days after linezolid discontinuation or ICU discharge whichever comes first

Collaborators and Investigators

• Sponsor: Helwan University
• Investigators: Principal Investigator: Mohamed Abdeltawab, Pharm D, Clinical pharmacy, 15 May hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): June 1, 2025

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Disease Attributes; Hematologic Diseases; Blood Platelet Disorders; Critical Illness; Thrombocytopenia; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Antioxidants; Protective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antidotes; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 11041990

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
• product manufactured in and exported from the U.S.: No