Experimental and Compassionate Drug Use During the First Wave of the COVID-19 Pandemic: A Retrospective Single-Center Study

Abstract

Introduction Concomitant experimental/compassionate drug administration has been all-pervasive in the treatment of COVID-19 patients. The objective of this study was to study the relationship between patient severity, the number of experimental/compassionate medications received (main outcome measure), and patient outcomes [survival to hospital discharge and length of hospital stay (LOS)]. Methods Retrospective analysis of data collected in real time during the first pandemic wave in a tertiary care hospital. Data included patient demographics, comorbidities, admission vital signs, laboratory values, most extreme respiratory intervention during hospitalization, and data regarding treatment with compassionate/experimental drugs during their stay. Results Overall, 292 PCR-confirmed patients with symptoms of COVID-19 were studied (March/April, 2020). Increasing respiratory support correlated with both LOS and mortality. Patients were more likely to receive more than 1 experimental/compassionate drugs as respiratory support escalated, ranging from 3% ( n = 4/136) among patients on room air to 77.3% ( n = 17/22) of mechanically ventilated/ECMO patients ( P < 0.001, linear by linear association). The mean number of experimental/compassionate drugs received also increased with escalating respiratory support ( P < 0.001, one-way ANOVA). After adjustment for severity of patient condition, administration of more experimental/compassionate drugs was unrelated to survival ( P = 0.24), but was related to increased LOS ( P < 0.001). Conclusion Patients that were hospitalized in worse condition were more likely to receive more experimental/compassionate drugs. Treatment was unrelated to survival but may have been related to LOS. This finding raises questions regarding the results of studies on medication effects that adjusted for multiple drug administration. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01890-9.

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Pneumonia

“…The lack of treatment effect in this subpopulation may be explained by the greater severity of the underlying COVID-19 lung disease reflected by the higher inspired oxygen requirements, lower lymphocyte counts and elevated inflammatory markers at baseline, which may, in turn suggest that there may be a threshold level for disease irreversibility. 20 Cox regression analysis demonstrated that mortality outcome differences in the FiO 2 <60% subpopulation between opaganib and placebo were independent of potential baseline characteristics confounders: in addition, the differences in severity between the 06/08/22 low FiO 2 (≤60%) and high FiO 2 (>60%) subpopulations were independent of disease duration.…”

“…The lack of treatment effect in this subpopulation may be explained by the greater severity of the underlying COVID-19 lung disease reflected by the higher inspired oxygen requirements, lower lymphocyte counts and elevated inflammatory markers at baseline, which may, in turn suggest that there may be a threshold level for disease irreversibility. 20…”

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

“…The use of hydroxychloroquine in intensive care unit (ICU) patients is an example of wasted resources, where these critically ill COVID-19 patients could have been included in other trials. In an interesting study regarding experimental and compassionate drug use during the first wave of the COVID-19 pandemic [ 69 ], the authors highlighted that this kind of treatment was unrelated to survival. A good conceptual model of the time-course of COVID-19 infection from the asymptomatic phase to more severe phases in patients who develop critical illness was proposed by Angriman et al [ 70 ].…”

“…That practice, without clear disclosure of duplicate reporting, may affect subsequent estimates and preclude valid meta-analyses. The authors of an interesting retrospective, single-center study regarding experimental and compassionate drug use during the first wave of the COVID-19 pandemic [ 69 ] demonstrated that the administration of multiple experimental/compassionate medications to the same patient not only does not improve survival rates but the true effect of any single drug remains questionable even after adjusting for the receipt of additional treatments. In these circumstances, it is more difficult to identify a potential cure.…”