Failed clinical trials on COVID-19 acute respiratory distress syndrome in hospitalized patients: common oversights and streamlining the development of clinically effective therapeutics

Morphological and functional findings in COVID-19 lung disease as compared to Pneumonia, ARDS, and High-Altitude Pulmonary Edema

“…A universal agreement on the use of corticosteroids in non-COVID ARDS is still lacking, but national guidelines started to consider the use of low-dose steroids in ARDS, while recommending against the use of high doses that may result in immune suppression and increased risk of opportunistic infections ( Tasaka et al, 2022 ). COVID-19 has boosted the pharmacological research investigating the role of several immunomodulating agents in respiratory failure, including steroids, anti-interleukin monoclonal antibodies and drugs with indirect action on the immune response ( Battaglini et al, 2022 ). While the use of steroids in hospitalized COVID-19 patients requiring oxygen supplementation is an established practice, these are typically contraindicated in initial, mild COVID-19.…”

“…While the use of steroids in hospitalized COVID-19 patients requiring oxygen supplementation is an established practice, these are typically contraindicated in initial, mild COVID-19. The use of other immunomodulating agents requires careful patient selection in COVID-19 and, more importantly, caution when translating to ARDS the findings of studies conducted in COVID-19 related respiratory failure ( Battaglini et al, 2022 ).…”

Challenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies

“…Several drugs have been tested to repair or limit alveolar epithelial damage, inflammation and immune response, edema and fibrosis, vascular remodeling, vascular permeability, and endothelial cell damage. Despite decades of investigating effective drug therapies for ARDS treatment, ARDS management remains mainly supportive with limited efficacy of the drugs explored in clinical practice and failed clinical trials [ 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , ...…”

“…The NCT02895191 trial is currently ongoing and will provide more information about ulinastatin; the NCT03089957 trial comparing ulinastatin versus usual ICU care in patients at risk of developing ARDS is also ongoing. Unfortunately, there is still no clear recommendation for statins, because the trials used the same doses that showed efficacy in healthy volunteers but in critically ill patients [ 150 ].…”

“…Surfactants act by reducing alveolar surface tension, thus preventing alveolar collapse and limiting pulmonary edema. Surfactants also have anti-inflammatory and antimicrobial properties [ 150 ]. Findings on the impact of surfactants on mortality in ARDS have been conflicting over years, and a recent meta-analysis concluded no significant improvement of mortality and gas exchange [ 129 ].…”