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.

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 ClinicalTrials.gov. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04497389; Pre-results.

Patient and Caregiver Attitudes toward Disorders of Sex Development Nomenclature.

PURPOSE: The medical terminology applied to differences/disorders of sex development has been viewed negatively by some affected individuals. A clinical population of patients with differences/disorders of sex development and their caregivers were surveyed regarding current nomenclature, hypothesizing that those unaffiliated with support groups would have more favorable attitudes. MATERIALS AND METHODS: We recruited English and Spanish speaking patients 13 years old or older with differences/disorders of sex development and their caregivers at 5 national tertiary care clinics from July 2016 to December 2018. No diagnoses were excluded. Participants completed a survey rating terminology commonly applied to differences/disorders of sex development. Responses were compared between subgroups, including members vs nonmembers of a support group. RESULTS: Of 185 potential participants approached 133 completed the survey (72% response rate). Congenital adrenal hyperplasia (33%) was the most common diagnosis. "Variation of sex development" was the most liked term (37%) but was not liked more significantly than "disorders of sex development" (27%, p=0.16). No term was liked by a majority of respondents. "Disorders of sex development" (37%) and "intersex" (53%) were the only terms most frequently viewed unfavorably. Support group members were significantly more likely to dislike the term "intersex" (p=0.02) and to like "variation of sex development" (p=0.02). CONCLUSIONS: A clinical population of patients and their caregivers had generally neutral attitudes toward nomenclature applied to differences/disorders of sex development. Members of a support group had clearer terminology preferences. "Variation of sex development" was the most liked term, and "disorders of sex development" and "intersex" were the most disliked. No term was liked by most respondents, and no clear alternative to the present nomenclature was identified.