Remdesiwir, hydroksychlorochina, lopinawir / rytonawir i interferon mają najprawdopodobniej niewielki lub zerowy wpływ na przebieg COVID-19 - wynika z badań przeprowadzonych na zlecenie Światowej Organizacji Zdrowia. Nieco więcej nadziei dają wyniki badań opublikowane w The New England Journal of Medicine (NEJM).
BACKGROUND WHO expert groups recommended mortality trials in hospitalized COVID-19 of four re-purposed antiviral drugs. METHODS Study drugs were Remdesivir, Hydroxychloroquine, Lopinavir (fixed-dose combination with Ritonavir) and Interferon-β1a (mainly subcutaneous; initially with Lopinavir, later not). COVID-19 inpatients were randomized equally between whichever study drugs were locally available and open control (up to 5 options: 4 active and local standard-of-care). The intent-to-treat primary analyses are of in-hospital mortality in the 4 pairwise comparisons of each study drug vs its controls (concurrently allocated the same management without that drug, despite availability). Kaplan-Meier 28-day risks are unstratified; log-rank death rate ratios (RRs) are stratified for age and ventilation at entry. RESULTS In 405 hospitals in 30 countries 11,266 adults were randomized, with 2750 allocated Remdesivir, 954 Hydroxychloroquine, 1411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4088 no study drug. Compliance was 94-96% midway through treatment, with 2-6% crossover. 1253 deaths were reported (at median day 8, IQR 4-14). Kaplan-Meier 28-day mortality was 12% (39% if already ventilated at randomization, 10% otherwise). Death rate ratios (with 95% CIs and numbers dead/randomized, each drug vs its control) were: Remdesivir RR=0.95 (0.81-1.11, p=0.50; 301/2743 active vs 303/2708 control), Hydroxychloroquine RR=1.19 (0.89-1.59, p=0.23; 104/947 vs 84/906), Lopinavir RR=1.00 (0.79-1.25, p=0.97; 148/1399 vs 146/1372) and Interferon RR=1.16 (0.96-1.39, p=0.11; 243/2050 vs 216/2050). No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation or hospitalisation duration. CONCLUSIONS These Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon, and are consistent with meta-analyses of mortality in all major trials. (Funding: WHO. Registration: [ISRCTN83971151], [NCT04315948]) ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN83971151, [NCT04315948] ### Funding Statement Funding was from WHO. No external funding was received. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics Committees in each country and WHO Ethics Review Committee All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes These are interim results. Once the final database is locked, data sharing requests will be considered. : /external-ref?link_type=ISRCTN&access_num=ISRCTN83971151 : /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04315948&atom=%2Fmedrxiv%2Fearly%2F2020%2F10%2F15%2F2020.10.15.20209817.atom
Remdesiwir lepszy niż nic
Nasze dane pokazują, że remdesiwir był lepszy od placebo pod względem skrócenia czasu powrotu do zdrowia u dorosłych, którzy byli hospitalizowani z powodu COVID-19 i mieli objawy infekcji dolnych dróg oddechowych - czytamy w publikacji NEJM.