Acute Infection

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.

The long-term goal is to test the clinical efficacy of senolytic therapies to reduce progression to and severity of sepsis in older patients. The central hypothesis is that a threshold burden of SnCs predisposes to a SASP mediated dysfunctional response to PAMPs, contributing to a disproportionate burden of sepsis in older patients. The study hypothesizes timely treatment with fisetin will interrupt this pathway. A multicenter, randomized, adaptive allocation clinical trial to identify the most efficacious dose of the senolytic fisetin to reduce the composite cardiovascular, respiratory, and renal sequential organ failure assessment score at 1 week, and predict the probability of success of a definitive phase III clinical trial.