Table 1.

Summary of Completed Clinical Trials using AF or AF-derived interventions.

Study	Condition	Reference/Group	Efficacy	Other Comments
“A pilot trial of human amniotic fluid for the treatment of COVID-19”	COVID-19	Selzman et al. 2021 [82,83] NCT04319731 Univ. of Utah	Higher dose patients had reduced C-reactive protein and improved clinical outcomes	Pilot study of 10 patients; 1 succumbed to COVID; last 6 patients received higher dose of AF; no AF-related AEs reported
“Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection”	COVID-19	Bellio et al. 2022 [84] NCT04657406	Potentially effective use of cfAF to prevent severe disease progression in at-risk patients.	Pilot study of 8 patients; no serious AEs reported.
“Effectiveness of Amniotic Fluid Injection in the Treatment of Trigger Finger: A Pilot Study”	Stenosing tenosynovitis	Quinet et al. 2020 [85] NCT03583151 Athens Orthopedic Group	Half of patients noted improvements and did not receive alternative treatment.	Study included 111 digits from 96 patients with a significant reduction in pain, triggering/day, and DASH score. No AEs or complications discovered based on injection of AF. Study found AF helpful for patients with diabetes, a vulnerable population to tenosynovitis.
“A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms”	Osteoarthritis (OA) of the knee	Farr et al. 2019 [86] Knee Preservation and Cartilage Restoration Center; Hospital of Special Surgery; Rush Univ., NYU Lagnone Med., Organogenesis, Inc.	Demonstrated safety and trends towards improved pain and function.	Included 200 patients randomized 1:1:1 (Amniotic suspension:Hyaluronic Acid:saline)
“A prospective study of 20 foot and ankle wounds treated with cryopreserved amniotic membrane and fluid allograft”	Wound healing	Werber et al. 2013 [87]	May represent useful option to treat chronic diabetic foot wounds.	Clinical study using granulized amniotic membrane and fluid to treat chronic diabetic foot wounds in 20 patients. Patients were followed for 12-weeks with 90% (18/20 subjects) of wounds healed. None of the wounds (0/20) progressed to amputation.
“Case Report: Administration of Amniotic Fluid-Derived Nanoparticles in Three Severely Ill COVID-19 Patients”	COVID-19	Mitrani et al. 2021 [88]	Treatment using cfAF appeared to be safe in n = 3 patients.	No adverse events associated with therapy. All three patients developed respiratory failure with hospitalization greater than 40 days and showed improved clinical status while in the ICU via resolution of acute delirium and reduction of inflammatory biomarkers.