Safety and Feasibility of Amniotic Fluid as a Treatment for COVID-19 Patients

A Phase I/II Randomized Double-blinded Placebo-controlled Clinical Trial to Determine Safety and Feasibility of Using an Acellular Sterile Filtered Amniotic Fluid as a Treatment for COVID-19 Patients

The purpose of this study is to explore the effectiveness of processed human amniotic fluid as a treatment for COVID-19.

Study Overview

• Status: Completed
• Conditions: SARS CoV-2
• Intervention / Treatment: Biological: Human Amniotic Fluid

Detailed Description

Past use of human amniotic products (i.e., membrane and fluid) has previously been FDA-approved as a human cells, Tissues, and Cellular and Tissue-Based Products (HCT/P) under 21 CFR 1271 for tissue injury; and has been used to reduce inflammation and fibrosis in patients with a variety of ailments. Given this, the investigators hypothesize that intravenously (IV) administered processed sterile filtered amniotic fluid will reduce inflammation in COVID-19 patients, and improve secondary clinical outcomes. Specifically, the investigators hypothesize that patients who receive IV administered hAF will see a 50% reduction in mean C-reactive protein levels following treatment.

Data sharing: Trial results will be published in peer reviewed publications upon completion of analysis.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Craig Selzman, MD; Phone Number: 8015815311; Email: craig.selzman@hsc.utah.edu
• Study Contact Backup: Name: Alyssa Messina, MA; Phone Number: 8015853752; Email: alyssa.messina@hsc.utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Age >18
2. SARS CoV-2 laboratory positive test, obtained within 14 days of enrollment
3. Hospitalized
4. COVID-19 symptomatic (cough, fevers, shortness of breath, and/or sputum production)
5. Has a room air pulse oximetry of ≤94% and requires supplemental oxygen therapy
6. Patients of childbearing potential who agree to use acceptable methods of contraception for 90 days after last administration of study investigational product (IP)
7. Patients who are receiving standard of care therapies for COVID-19 that are not FDA approved are eligible for this study
8. Subjects must be able to consent to the study (i.e., Glasgow Coma Scale score of ≥14)
9. Patients are required to have controlled blood pressure of <160/96 and a pulse of <110.

Exclusion criteria:

1. Patients on invasive mechanical ventilation (e.g., endotracheal intubation)
2. Chronic home oxygen utilization
3. Home or current use of immunosuppressive medications (including steroids)
4. Women who are pregnant, breastfeeding, or become pregnant during the study
5. Patients on non-invasive positive pressure ventilation
6. Patients on >12 liters per minute via non-rebreather (NRB) or >80% oxygen via high flow nasal cannula
7. Patients who, in the opinion of the PI, have impending respiratory failure, defined as requiring rapidly escalating oxygen supplementation
8. Patients with a hemoglobin <9 mg/dL
9. Patients diagnosed with Stage 4 or 5 chronic kidney disease (CKD)
10. Patients with diagnosed New York Heart Association (NYHA) class 4 or 5 congestive heart failure
11. Patients with a left ventricular assist device (LVAD)
12. Patients with thromboembolic phenomena
13. Patients with Type 2 and above heart block
14. Patients with established positive bacterial blood cultures prior to enrollment
15. Patients with ongoing pericardial effusion or ascites
16. Patients with clinically significant arrhythmia
17. Patients with liver function tests (ALT or AST) >3x normal
18. Patients with untreated HIV infection
19. Patients diagnosed with end-stage organ disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 10ml intravenous hAF QD (once daily) for 5 consecutive days	Biological: Human Amniotic Fluid; Patients will receive 10ml intravenous hAF each day for 5 consecutive days.
No Intervention: Standard of Care; 10 mL normal saline QD (once daily) for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reactive Protein	Assess reduction of inflammation in COVID-19 patients, potentially leading to a decrease in the need for critical care. This will be assessed by measurement of C-reactive protein levels before and after the intervention. Units: mg/dL	Baseline through post-treatment (6 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for ECMO	Comparison of ECMO incidence between intervention and control groups	From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
Death Within 30 Days	Comparison of mortality between intervention and control groups	Baseline through 30 days
Any ICU Admission	Comparison of ICU admissions between intervention and control groups	Baseline through 30 days
Hospital Length of Stay	Comparison of days spent in hospital between intervention and control groups	From date of hospital admission through date of discharge or death, whichever comes first (up to 100 days)
Need for Invasive Mechanical Ventilation	Comparison of mechanical ventilation incidence between intervention and control groups	From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
Biomarker Levels (Interleukin-6)	Comparison of mean biomarker level change between intervention and control groups. Units: pg/mL	Baseline through post-treatment (6 days)
Biomarker Levels (D-dimer)	Comparison of mean biomarker level change between intervention and control groups. Units: mg/mL	Baseline through post-treatment (6 days)
Biomarker Levels (Lactate Dehydrogenase)	Comparison of mean biomarker level change between intervention and control groups. Units: u/L	Baseline through post-treatment (6 days)
Major Adverse Cardiac Events	Compare frequency of major adverse cardiac events (MACE) between intervention and control groups	From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
Patient-reported Functional Status at 1 Month	Comparison of PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire results on a computer-adaptive platform between intervention and control groups using T-scores. Scale mean = 50, standard deviation = 10. Higher scores indicate more of the concept being measured (i.e., physical function = a higher score indicates better outcomes; dyspnea severity, sleep disturbance, anxiety = a higher score indicates worse outcomes). Sleep Disturbance, Dyspnea Severity, Anxiety Less than 55 = None to slight/Within normal limits 55.0-59.9 = Mild 60.0-69.9 = Moderate 70 and over = Severe Physical Function 55 and over = Within normal limits 54.9-40 = Mild limitations 39.9-30 = Moderate limitations 29.9 and below = Severe limitations	1 month post-discharge
Patient-reported Functional Status at 3 Months	Comparison of PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire results on a computer-adaptive platform between intervention and control groups using T-scores. Scale mean = 50, standard deviation = 10. Higher scores indicate more of the concept being measured (i.e., physical function = a higher score indicates better outcomes; dyspnea severity, sleep disturbance, anxiety = a higher score indicates worse outcomes). Sleep Disturbance, Dyspnea Severity, Anxiety Less than 55 = None to slight/Within normal limits 55.0-59.9 = Mild 60.0-69.9 = Moderate 70 and over = Severe Physical Function 55 and over = Within normal limits 54.9-40 = Mild limitations 39.9-30 = Moderate limitations 29.9 and below = Severe limitations	3 months post-discharge
Patient-reported Functional Status at 6 Months	Comparison of PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire results on a computer-adaptive platform between intervention and control groups using T-scores. Scale mean = 50, standard deviation = 10. Higher scores indicate more of the concept being measured (i.e., physical function = a higher score indicates better outcomes; dyspnea severity, sleep disturbance, anxiety = a higher score indicates worse outcomes). Sleep Disturbance, Dyspnea Severity, Anxiety Less than 55 = None to slight/Within normal limits 55.0-59.9 = Mild 60.0-69.9 = Moderate 70 and over = Severe Physical Function 55 and over = Within normal limits 54.9-40 = Mild limitations 39.9-30 = Moderate limitations 29.9 and below = Severe limitations	6 months post-discharge
Patient-reported Functional Status at 12 Months	Comparison of PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire results on a computer-adaptive platform between intervention and control groups using T-scores. Scale mean = 50, standard deviation = 10. Higher scores indicate more of the concept being measured (i.e., physical function = a higher score indicates better outcomes; dyspnea severity, sleep disturbance, anxiety = a higher score indicates worse outcomes). Sleep Disturbance, Dyspnea Severity, Anxiety Less than 55 = None to slight/Within normal limits 55.0-59.9 = Mild 60.0-69.9 = Moderate 70 and over = Severe Physical Function 55 and over = Within normal limits 54.9-40 = Mild limitations 39.9-30 = Moderate limitations 29.9 and below = Severe limitations	12 months post-discharge

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Craig Selzman, MD, University of Utah

Publications and helpful links

General Publications

• Tonna JE, Pierce J, Hatton N, Lewis G, Phillips JD, Messina A, Skidmore CR, Taylor K, Selzman CH. 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Actual): August 2, 2022
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Amniotic fluid
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 132922

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes