Amantadine in unvaccinated patients with early, mild to moderate COVID‐19: A randomized, placebo‐controlled, double‐blind trial

Abstract

AbstractBackground and purposeAdamantanes were listed as an interesting option as an early intervention against COVID‐19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID‐19 and its neurological sequelae.MethodsUnvaccinated patients with confirmed SARS‐CoV‐2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI‐WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15.ResultsWe enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI‐WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI‐WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated.ConclusionThe central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID‐19 patients.