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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
Lopinavir/ritonavir is approved by FDA against HIV as an oral combination therapy. In vitro activity of the combination has also been proved against some CoVs by inhibiting 3-chymotrypsin-like protease activity [22]. Limited data is available on the efficacy of the Lopinavir/ritonavir when used in combination against SARS and MERS. It was also demonstrated in trials that its administration at early peak replication phase, i.e., within 7–10 days is beneficial while delayed initiation of the therapy has no effects [23]. Animal trials of combination of Lopinavir/ritonavirin against MERS-CoV was effective [20]. Based on previous results, it was selected for use against COVID-19. A study including 199 hospitalized patients with severe COVID-19 symptoms did not show significant clinical improvement or mortality when compared to conventional care [24]. However, it has been a part of a number of trials against COVID-19 including a two arms SOLIDARITY trial in which it was tested in combination with and without of the addition interferon-β and has been recommended as a possible therapy for against COVID-19 [25].
Clinical Trials of COVID-19 Therapeutics and Vaccines
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Candan Hizel Perry, Havva Ö. Kılgöz, Şükrü Tüzmen
In keeping with drug repurposing investigations, several drugs, including remdesivir, HCQ, Kaletra (lopinavir/ritonavir) [46], favipiravir [47], ivermectin, (TCZ) tocilizumab, dexamethasone, and colchicine [48] have been studied in different multi-national and multi-armed trials, to assess their clinical efficacy for COVID-19 treatment, and can be found at ClinicalTrials.gov with National Clinical Trial (NCT) identifiers. While some of these clinical trials are already completed, others are still ongoing and recruiting. Selected compelling examples of repurposed drugs in clinical trials are listed in Table 14.2. Among these repurposed drugs, in particular remdesivir and HCQ, have been the center of attention. However, the SOLIDARITY trial (NCT04315948) is one of the largest international randomized trials launched by the WHO and partners, enrolling almost 12,000 patients at 500 hospital sites across 30 countries. This trial evaluated the clinical effectiveness of remdesivir/lopinavir/ritonavir/HCQ together with Interferon β-1A on three important outcomes: mortality, need for assisted ventilation, and duration of hospital stay. The outcome was that all four evaluated treatments showed little or no effect on overall mortality, initiation of ventilation, or duration of hospital stay in hospitalized patients, as presented in an interim report [46].
The use of antiviral drugs in children
Published in Journal of Chemotherapy, 2022
Marco Antonio Motisi, Agnese Tamborino, Sara Parigi, Luisa Galli, Maurizio de Martino, Elena Chiappini
Several molecules with safety profiles that were already known because they had been used previously to treat other types of pathologies have been used since the start of the pandemic. The SOLIDARITY trial, an ongoing multicentre randomised clinical trial conducted by the World Health Organization (WHO), assessed four different molecules (remdesivir, hydroxychloroquine, lopinavir/ritonavir, and interferon β1a) for the treatment of COVID-19. The trial included 11,330 adult patients in 30 countries, randomly assigned to receive one of the four experimental treatments or the care standard, with open control. To date, none of these drugs has been proven to clearly benefit the course of the and mortality [39]. In particular, hydroxychloroquine and protease inhibitors (lopinavir/ritonavir or darunavir/cobicistat) have not proven sufficiently effective for the treatment of COVID-19; preliminary results of clinical trials have already shown little or no reduction in mortality in hospitalized patients compared with standard care, and the use of these drugs is therefore not recommended outside the experimental setting (hydroxychloroquine rate ratio 1.19; 95% CI 0.89–1.59 P = 0.23 – lopinavir/ritonavir rate ratio 1.00; 95% CI, 0.79–1.25 P = 0.97) [39,40]. The combination of hydroxychloroquine and remdesivir should be discouraged, as it may reduce the antiviral activity of the latter [41]. In addition, hydroxychloroquine significantly increases the risk of QT interval prolongation, and the extent of QT interval prolongation is greater when combined with azithromycin [42].
The use of remdesivir for the management of patients with moderate-to-severe COVID-19: a systematic review
Published in Expert Review of Anti-infective Therapy, 2022
Kaeshaelya Thiruchelvam, Chia Siang Kow, Muhammad Abdul Hadi, Syed Shahzad Hasan
The open-label multicentre Solidarity trial by the WHO reported outcomes on in-hospital mortality, as well as the initiation of mechanical ventilation and hospital duration, with several investigational agents [28]. This study included 11,330 patients from 405 hospitals in 30 countries [28]. Trial drugs included remdesivir, hydroxychloroquine, lopinavir, and interferon, where a 10-day duration of remdesivir with a 200 mg intravenous loading dose, followed by a 9-day regimen of 100 mg was used; doses of other drugs are reported in the summary table. There were no placebos used in this study. None of the trial drugs, including remdesivir, reduced the requirement for ventilation for patients who were already on it. In addition, none of the trial drugs including remdesivir reduced duration of hospitalization.
Antiviral treatment selection for SARS-CoV-2 pneumonia
Published in Expert Review of Respiratory Medicine, 2021
Matteo Bassetti, Silvia Corcione, Silvia Dettori, Andrea Lombardi, Tommaso Lupia, Antonio Vena, Francesco Giuseppe De Rosa, Andrea Gori, Daniele Roberto Giacobbe
Preliminary data have also been provided by the WHO Solidarity trial, a large, global, open-label randomized study involving over 11,000 COVID-19 patients in 405 hospitals in over 30 countries [40]. RDV was one of the four treatment alternatives (with lopinavir/ritonavir, hydroxychloroquine, and interferon beta-1a), each compared with standard care, and the primary outcome was in-hospital mortality. Secondary outcomes were the initiation of ventilation and the duration of hospitalization [40]. None of the four treatments showed any benefit, although one limitation was a lack of data on the duration of symptoms before RDV initiation, and the direction of the effect in the subgroup of patients not requiring invasive ventilation treated with RDV was toward improved survival (see expert opinion below) [40].