Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial

Abstract

BackgroundClarithromycin clinical efficacy has not been described in COVID-19.Research questionIs oral clarithromycin beneficial for treating patients diagnosed with COVID-19?Study and methodsAn open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted at four study sites in Greece between May and October 2020. Ninety participants with respiratory tract infections received clarithromycin 500 mg every 12 hours for 7 days; another 90 standard-of-care (SOC) propensity score-matched concurrent controls received azithromycin plus hydroxychloroquine. The composite primary endpoint was defined for patients with upper respiratory tract infection as: (a) no need for hospital re-admission or (b) lack of progression into lower respiratory tract infection and, for patients with lower respiratory tract infection, as at least 50% decrease of the score of respiratory symptoms at the end-of-treatment (EOT) without progression into severe respiratory failure (SRF). The incidence SRF at the test-of-cure (TOC) on day 14 was a secondary endpoint. For clarithromycin-treated patients, viral load of SARS-CoV-2, biomarkers, the function of mononuclear cells, and safety were assessed; biomarkers were also measured in SOC comparators.ResultsThe primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%) and 73.3% of concurrent SOC comparators (95%CIs; 63.4-81.4%). The odds ratio for the primary endpoint with clarithromycin treatment in univariate analysis was 2.36 (95%CIs 1.09-5.08; P: 0.039). Results were confirmed after multivariate stepwise logistic regression analysis (odds ratio 3.30; 95% CI 1.10-9.87; P: 0.033). At the TOC visit, the incidence of SRF was 12.2% (n = 11 ; 95%CIs 6.9-20.6%) among patients treated with clarithromycin (odds ratio for SRF 0.38; 95%CIs 0.17-0.84) versus 26.7% (n= 24; 95%CIs 18.6-36.6%) among concurrent SOC comparators (P: 0.023). Clarithromycin use was associated with decreases in circulating levels of C-reactive protein, of tumour necrosis factor-alpha and of interleukin (IL)-6; by an increase of the ratio of Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 relative viral load. No safety concerns were reported. Patients starting clarithromycin with the first five days from symptoms onset achieved better responses.InterpretationClarithromycin treatment is associated with early clinical improvement in patients with moderate COVID-19. Modulation of the Th1/Th2 responses is proposed as the mechanism of action.Trial RegistrationClinicalTrials.gov, NCT04398004

Diverse effects of clarithromycin and proposal of its clinical application for treating COVID-19 as a repurposing drug

“…In this article, the antiviral effect of CAM on SARS-CoV-2 and its immunomodulatory effect in COVID-19 treatment were discussed and emphasized. The recent ACHIEVE clinical trial (Tsiakos et al, 2020)…”

“…An open-labeled non-randomized clinical trial using CAM for treating COVID-19 as a single agent (i.e., ACHIEVE) started in Greece in May, 2020. Just recently, the results, though preprint, were published in medRxiv (Tsiakos et al, 2020). Almost at the same time, Mansilla et al (2020) started up the "Macrolides-Clarithromycin Task-Force for the Treatment and Prophylaxis of COVID-19 as a single agent".…”

Mini Review on Different Analytical Approaches Applied on some Selected GIT acting Combination

“…Recently, CLR has had a clear role in the treatment of the CO VI d 19 protocol. (29,30). LAN (lansoprazole) is a drug that lowers stomach acid.…”

The Role of Macrolides for the Management of Community-Acquired Pneumonia and Pneumonia by the Novel Coronavirus SARS-CoV-2 (COVID-19): A Position Paper by Four Medical Societies from Greece

“…As a consequence, there may be a window over the time course of COVID-19 where the use of macrolides is of major benefit. [34]. The primary study endpoint was defined as at least 50% decrease of the respiratory symptoms score for participants with lower respiratory tract infection or as no hospital readmission for participants with upper respiratory tract infection.…”