Sepsis, Acute Infection, Severe Infection
Conditions
Keywords
Sepsis, Acute Infection, Severe Infection, Acetylcysteine, Liver dysfunction
Brief summary
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.
Interventions
Intravenous infusion of N-acetylcysteine (200 mg/kg mixed with normal saline to a final volume of 500 ml) administered over four hours.
Sponsors
Theis S. Itenov
University Hospital Bispebjerg and Frederiksberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data Safety and Monitoring Board.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Days alive and out of hospital at 14 days post-randomization (DAOH-14) | Assessed 14 days post-randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Assessed at 14 days post-randomization | 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. |
Countries
Denmark
Contacts
CONTACTFrans Wiberg, MD
CONTACTTheis S Itenov, MD, PhD
Outcome results
None listed