A randomized, double-blinded, placebo-controlled clinical trial of sterile filtered human amniotic fluid for treatment of COVID-19

Abstract

Abstract Importance Acellular human amniotic fluid (hAF) is an antimicrobial and anti-inflammatory fluid that has been used to treat various pro-inflammatory conditions. In a feasibility study, we have previously demonstrated that hAF could be safely administered to severely ill patients with coronavirus disease-19 (COVID-19). The impact of acellular hAF on markers of systemic inflammation and clinical outcomes during COVID-19 infection remain unknown. Objective To determine the safety and efficacy of acellular, sterile processed intravenously administered hAF on markers of systemic inflammation during COVID-19. Design, settings and participants This single-center Phase I/II randomized, placebo controlled clinical trial enrolled adult (age ≥ 18 years) patients hospitalized for respiratory symptoms of COVID-19, including hypoxemia, tachypnea or dyspnea. The study was powered for outcomes with an anticipated enrollment of 60 patients. From 09/28/2020 to 02/04/2022 we enrolled and randomized 47 (of an anticipated 60) patients hospitalized due to COVID-19. One patient withdrew consent after randomization but prior to treatment. Safety outcomes to 30 days were collected through hospital discharge and were complete by the end of screening on 6/30/2022. Interventions Intravenous administration of 10 cc sterile processed acellular hAF once daily for up to 5 days vs placebo. Main outcome and measures Blood biomarkers of inflammation, including C-Reactive protein (CRP), lactate dehydrogenase, D-dimer, and interleukin-6 (IL-6), as well as safety outcomes. Results Patients who were randomized to hAF (n = 23) were no more likely to have improvements in CRP from baseline to Day 6 than patients who were randomized to placebo (n = 24) hAF: -5.9 [IQR -8.2, -0.6] vs placebo: -5.9 [-9.4, -2.05]; p = 0.6077). There were no significant differences in safety outcomes or adverse events. Secondary measures of inflammation including lactate dehydrogenase, D-dimer and IL-6 were not statistically different from baseline to day 6. Conclusions and relevance In this randomized clinical trial involving hospitalized patients with COVID-19, the intravenous administration of 10 cc of hAF daily for 5 days did not result in statistically significant differences in either safety or markers of systemic inflammation compared to placebo, though we did not achieve our enrollment target of 60 patients. Trial registration This trial was registered at ClinicalTrials.gov as #NCT04497389 on 04/08/2020.