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This combination regimen serves as the standard-of-care (SOC) control arm in clinical trials evaluating treatments for severe COVID-19 and Acute Respiratory Distress Syndrome (ARDS), notably in a Phase 1/2 trial (NCT04390152) sponsored by BioXcellerator. The protocol typically involves the administration of hydroxychloroquine (an antimalarial with immunomodulatory properties), the protease inhibitor combination lopinavir/ritonavir (originally developed for HIV), or the macrolide antibiotic azithromycin, alongside a placebo in place of the experimental intervention (such as mesenchymal stem cells). These agents were repurposed during the early COVID-19 pandemic based on in vitro antiviral activity or anti-inflammatory effects, though their clinical efficacy in this context has been widely debated and largely superseded by newer standards of care.
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