[Clinical trials approved by Aifa for Covid-19: report of the main results to fill the unmet medical need.].

Introduction: the rapidity with which the Coronavirus epidemic emergency exploded took the scientific community by surprise, unprepared for such an event. The objective of this work is to evaluate, to date, the state of the art of the clinical trials approved by Aifa, analyzing the characteristics of the single completed and published trials and the authorization status for the use of the drugs under study in the treatment of Covid-19.

Materials And Methods: The protocols available for each clinical study were extrapolated from the Aifa website relating to the management of clinical trials in Italy during the Covid-19 emergency; the unique EudraCT and Nct codes were extrapolated from these, verifying their publication using the PubMed search engine, the ClinicalTrials.gov platform, the EU Clinical Trials Register portal and the website of the pharmaceutical company identified as the promoter of the study. The characteristics of the individual trials useful for the analysis were extracted from the published papers. Finally, a comparison was made between the studies relating to experimental drugs which were subsequently authorized for the Covid-19 indication and the studies relating to drugs which have not yet been authorized to date.

Results: In total, Aifa approved 94 between March 2020 and March 2022; of these, 22 are not listed on ClinicalTrials.gov; of the 72 trials listed on ClinicalTrials.gov, 31 (43%) were published, for a total of 25 drugs. Of the authorized and published trials, 26 report the "mortality endpoint". The most studied drugs are remdesivir and tocilizumab with 3 studies each, methylprednisone and molnupravir with 2. 14 studies are phase III, of these 12 used a drug as an experimental treatment which was then approved for Covid-19. Of the 41 trials present on ClinicalTrials.gov that have not yet been published, 21 are terminated. The drugs anakinra, remdesivir, molnupravir, regdanvimab, tocilizumab, AZD1222 vaccine have been updated/registered for Covid-19 indication; anakinra, baricitinib, tocilizumab and sarilumab have been included in the list of Law 648/96; remdesivir, canakinumab and ruxolitinib have been entered into compassionate use programmes.

Discussion And Conclusions: The methods of early access to therapy have allowed an alternative to patients who are not eligible for the ongoing trials. The challenge that the scientific community has faced has strengthened the culture of evidence-based medicine.