Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial

BMJ Open. 2021 Feb 11;11(2):e045162. doi: 10.1136/bmjopen-2020-045162.


Introduction: Human amniotic fluid (hAF) has been shown to reduce inflammation in multiple experimental models. hAF has previously been approved by the US Food and Drug Administration (FDA) as a human cellular and tissue product for tissue injury for human administration, and used safely in thousands of patients as a therapeutic treatment for diverse conditions. Given the profound inflammatory response observed in patients with COVID-19, and the successful completion of 10-patient pilot study of intravenous hAF, we present a trial design for a larger clinical trial of intravenous hAF for the treatment of COVID-19.

Methods and analysis: This paper describes the methodology of a phase I/II randomised, double-blinded, placebo-controlled clinical trial to determine the safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19. Primary outcome will be the change in C-reactive protein. Secondary outcomes include safety, biomarker inflammatory levels and clinically relevant outcomes at 30 days, including mortality, ventilator-free days and hospital and intensive care unit length of stay. Exploratory outcomes of health-related quality-of-life patient-reported outcomes will be collected. Hospitalised patients with laboratory-confirmed COVID-19 will be recruited.

Ethics and dissemination: This study was approved by the University of Utah Institutional Review Board (IRB_0013292), approved by the US FDA under Investigational New Drug (No 23369) and is registered on Results will be disseminated via peer-reviewed publications and conference presentations.

Trial registration number: NCT04497389; Pre-results.

Keywords: COVID-19; clinical trials; intensive & critical care; respiratory medicine (see thoracic medicine).

Publication types

  • Clinical Trial Protocol
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid*
  • Biological Products / therapeutic use*
  • C-Reactive Protein / analysis
  • COVID-19 / therapy*
  • Double-Blind Method
  • Feasibility Studies
  • Humans
  • Inflammation / therapy
  • Pilot Projects
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Biological Products
  • C-Reactive Protein

Associated data