Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke – A Randomized controlled trial (NACTLYS)

Abstract

Abstract Background There is a clinical need for thrombolytic agents that can disaggregate arterial thrombi without significantly increasing the risk of bleeding. The present study was aimed to study if adjunctive therapy with N-acetylcysteine (NAC) along with standard thrombolytic agent was safe and effective in patients with acute ischemic stroke as thrombolytic agent. Methods An open label randomized blinded assessor pilot study was conducted. Patients with acute ischemic stroke presented to the emergency within 4.5 hours were randomized into two groups and intravenous NAC with intravenous tissue plasminogen activator (IV tPA) or IV tPA alone was given in a 1:1ratio. Primary outcomes were any intracerebral hemorrhage or symptomatic cerebral hemorrhage, any major or minor systemic bleeding and any adverse reactions. Secondary outcomes were major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 hours, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 hours, modified Rankin scale and mortality at 3 months of follow-up. Results A total of 40 patients were enrolled out of which 21 patients received rtPA only and 19 patients received NAC with alteplase. There was no significant difference in baseline characteristics among both the groups. Among primary outcomes, no significant difference was noted in the adverse events(p=0.99), intracranial hemorrhage(p=0.21), symptomatic intracerebral hemorrhage (p=0.47) and extracranial bleeding (p=0.21). Among the secondary outcomes, median NIHSS at 24 hours was significantly low in the control arm (p=0.03). The proportion of patients with mRS 0-2 at 3 months and mortality at 3 months was comparable among both the groups (p=0.85 and p=0.99 respectively). Conclusion N-acetylcysteine as an adjunct to alteplase has not shown significant difference in morbidity, mortality at3months and safety profile. However, there was slightly better early neurological outcome with co- administration of N-acetylcysteine and alteplase. These indifference might be due to the small size of the present study. Future larger trials are needed to further conclude on safety and efficacy of N-acetylcysteine as a thrombolytic agent.