Individualized Multiplex Pathophysiological Treatment of Severe Acute Infections: N-Acetylcysteine

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.

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)