Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study.

BACKGROUND: Amantadine has been proposed as a treatment for COVID-19 because it shows anti-SARS-CoV-2 activity in vitro. However, to date, no controlled study has assessed the safety and efficacy of amantadine in COVID-19. RESEARCH QUESTION: Whether amantadine is effective and safe among patients with different COVID-19 severity classifications. STUDY DESIGN: and Methods: This was multi-centre, randomised, placebo-controlled study.Patients with oxygen saturation ≤94% and no need for high-flow oxygen or ventilatory support were randomly allocated to receive oral amantadine or placebo (1:1) for 10 days in addition to standard care. The primary endpoint was time to recovery assessed over 28 days since randomisation, defined as discharge from hospital or no need for supplemental oxygen. RESULTS: The study was terminated early due to a lack of efficacy after an interim analysis. Final data from 95 patients who received amantadine (mean age, 60.2 years; 65% male; 66% with comorbidities) and 91 patients who received placebo (mean age, 55.8 years; 60% male; 68% with comorbidities) were obtained. The median (95% CI) time to recovery was 10 days both in the amantadine (9-11) and placebo arms (8-11; subhazard ratio = 0.94 [95%CI 0.7-1.3]). The percentage of deaths and percentage of patients who required intensive care at 14 and 28 days did not significantly differ between the amantadine and placebo groups. INTERPRETATION: Adding amantadine to standard care in patients hospitalised with COVID-19 did not increase the likelihood of recovery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04952519; www. CLINICALTRIALS: gov.

The efficacy of amantadine hydrochloride in the treatment of COVID-19 - a single-center observation study.

Coronavirus disease 19 (COVID-19) rapidly spread worldwide. The search for effective measures to counter the development and effects of the pandemic includes: identifying the disease pathogen, introducing methods of reducing its transmission, building the population immunity, and the search for a cure, both among the new and already-known substances with potential antivirus activity such as amantadine hydrochloride. AIM: The aim of the study was an observational single-center analysis of confirmed COVID-19 cases treated with amantadine in ambulatory settings. MATERIALS AND METHODS: The 55 patients with confirmed COVID-19 diagnosis were treated in ambulatory settings by amantadine with a treatment schema varied from 200 mg to 500 mg per day. A retrospective analysis was based on symptoms, hospitalization, and number of deaths. RESULTS: The mean age of the patients was 55.9 years (SD=15), and most patients were male (60%). Despite the majority of patients 64% (n=35) suffering from comorbidities and 53% (n=29) of patients having been diagnosed with pneumonia, none of them died, and only four had required hospitalization in the course of COVID-19. Clinical stabilization was achieved in 91% (n=50) of patients within 48 hours after the first dose of amantadine with further improvement; additionally, all patients experienced remission of COVID-19. In total, 93% (n=51) of patients did not require hospitalization during the treatment. CONCLUSIONS: The data may suggest that amantadine hydrochloride shows efficacy in preventing hospitalization and deaths in patients with COVID-19. At the same time, it emphasizes that daily monitoring of the patient and regular examination are important in the case of SARS-CoV-2 infection dynamics. It may be justified to carry out a prospective, randomized, and double-blinded clinical study with the postulated amantadine scheme.

[Fractal dimension--a new EEG-based method of assessing the depth of anaesthesia]. / Próba wykoraystania analizy sygnalów EEG metoda wymiaru fraktalnego do okreslania stopnia zniesienia swiadomosci podczas indukcji znieczulenia ogólnego.

BACKGROUND: It has been suggested that analysis of the EEG signal using the fractal dimension method may be useful for assessment of depth of anaesthesia. METHODS: Thirty ASA I and II patients, scheduled for elective surgery under general anaesthesia were induced with midazolam, fentanyl and propofol and paralyzed with rocuronium or cis-atracurium. Clinical signs of the depth of anaesthesia were classified to one of five OAA/S levels. Standard vital parameters were observed and brain electrical activity was measured using the bispectral index (BIS) and burst suppression ratio (BSR). The EEG signal was recorded and processed postoperatively to calculate Higuchi's fractal dimension (FD). The latter was presented as a derivative: (D(F)-1) x 100. RESULTS: Mean correlation coefficients between OAA/S scale levels, and BIS and (D(F)-1) x 100 values, were respectively: 0.749+/-0.172 and 0.753+/-0.220. In 28 (93.3%) patients, BIS correlated well with FD (r=0.63+/-0.33). In twenty cases, burst suppression occurred and the correlation coefficient between BIS and DF was much lower (r=0.5860+/-3650), when compared to the group of 10 patients in which no burst suppression was detected (r=0.711+/-0.251). Appropriate correction was made using the following formula: D(FK)=D(F)-(D(F) x BSR). The mean correlation coefficient between BIS values and D(FK) in the BS group was r=0.629+/-0.331. In all cases, the mean correlation coefficient between (D(F)-1) x 100 and BIS was r=0.661+/-0.307 (p<0.001). CONCLUSIONS: The fractal dimension method can be regarded as equal to BIS for assessment of depth of anaesthesia.