Individualized Multiplex Pathophysiological Treatment of Severe Acute Infections: N-Acetylcysteine (IMPACT-NAC)

A Randomized, Placebo-controlled, Blinded, Parallel-group Clinical Trial to Assess the Efficacy of N-acetylcysteine in Adults With Acute Infections or Sepsis and Evidence of Liver Dysfunction: the IMPACT-NAC Trial

The primary objective of the IMPACT-NAC trial is to assess the effects of N-acetylcysteine on survival and hospital length of stay in adults admitted to the emergency department with acute infection or sepsis and evidence of liver dysfunction.

The main question it aims to answer is: does N-acetylcysteine increase the number of days alive and out of the hospital within the first 14 days after enrolment in the trial?

To answer this question, we will conduct a randomized, double-blinded controlled trial of 360 participants.

Participants will be randomized to either N-acetylcysteine or placebo (normal saline without active drugs). This will be administered as an infusion during four hours within the first day of hospital admission.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Severe Infection; Acute Infection
• Intervention / Treatment: Drug: N-Acetylcysteine (NAC) Treatment

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Frans Wiberg, MD; Phone Number: +4528741294; Email: frans.wiberg@regionh.dk
• Study Contact Backup: Name: Theis S Itenov, MD, PhD; Email: theis.skovsgaard.itenov@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Department of Emergency Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg
    • Contact: Jens H Rasmussen, MD; Phone Number: +4526198801; Email: jens.henning.rasmussen@regionh.dk
    • Principal Investigator: Jens H Rasmussen, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

1. Age ≥18 years
2. Documented clinical suspicion of infection
3. Model for end-stage liver disease (MELD) score ≥9

Exclusion criteria

1. Admitted to hospital >24 hours before randomization
2. Any previous severe anaphylaxis
3. Other known allergy to N-acetylcysteine
4. Ongoing treatment with N-acetylcysteine at randomization
5. Documented clinical suspicion of bile duct obstruction
6. Refractory circulatory shock
7. Informed consent not obtainable
8. Inability to read and understand Danish to a degree that allows valid informed consent and completion of trial assessments
9. Involuntary admission under the psychiatric law
10. Expected initiation of palliative care within 48 hours of randomization
11. Ongoing treatment with nitroglycerin
12. Any other condition deemed by the investigator to compromise patient safety or trial integrity (e.g., severe coagulopathy, uncontrolled bleeding, diabetic ketoacidosis)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetylcysteine	Drug: N-Acetylcysteine (NAC) Treatment; Intravenous infusion of N-acetylcysteine (200 mg/kg mixed with normal saline to a final volume of 500 ml) administered over four hours.
No Intervention: Placebo (normal saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Days alive and out of hospital at 14 days post-randomization (DAOH-14)	Assessed 14 days post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with one or more serious adverse event within 14 days of randomization		Assessed 14 days post-randomization
All-cause mortality at day 180		Assessed at 180 days post-randomization
Health-related quality of life (HRQoL) at day 180 using EQ-5D-5L		Assessed 180 days post-randomization
Admission to an intensive care unit (ICU) within 14 days of admission		Assessed at 14 days post-randomization
Duration of antibiotic therapy from randomization to day 14		Assessed at 14 days post-randomization
Time to clinical stability	Number of days from randomization to first occurrence of clinical early warning score (C-EWS) ≤1. For participants with registered chronic elevated C-EWS parameters, the adjusted score will be used.	Assessed at 14 days post-randomization

Collaborators and Investigators

• Sponsor: Theis S. Itenov
• Collaborators: University Hospital Bispebjerg and Frederiksberg

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Actual): December 9, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sepsis; Acute Infection; Acetylcysteine; Severe Infection; Liver dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Infections; Liver Diseases; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Amino Acids; Cysteine; Amino Acids, Sulfur; Acetylcysteine; Therapeutics
• Other Study ID Numbers: IMPACT-NAC-01; 2026-525895-25-00 (Ctis)

Drug and device information, study documents

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