SARS CoV-2
Conditions
Keywords
Amniotic fluid, COVID-19
Brief summary
The purpose of this study is to explore the effectiveness of processed human amniotic fluid as a treatment for COVID-19.
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.
Interventions
BIOLOGICALHuman Amniotic Fluid
Patients will receive 10ml intravenous hAF each day for 5 consecutive days.
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-reactive Protein | Baseline through post-treatment (6 days) | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Any ICU Admission | Baseline through 30 days | Comparison of ICU admissions between intervention and control groups |
| Hospital Length of Stay | From date of hospital admission through date of discharge or death, whichever comes first (up to 100 days) | Comparison of days spent in hospital between intervention and control groups |
| Need for Invasive Mechanical Ventilation | From date of enrollment through date of discharge or death, whichever comes first (up to 100 days) | Comparison of mechanical ventilation incidence between intervention and control groups |
| Biomarker Levels (Interleukin-6) | Baseline through post-treatment (6 days) | Comparison of mean biomarker level change between intervention and control groups. Units: pg/mL |
| Biomarker Levels (D-dimer) | Baseline through post-treatment (6 days) | Comparison of mean biomarker level change between intervention and control groups. Units: mg/mL |
| Biomarker Levels (Lactate Dehydrogenase) | Baseline through post-treatment (6 days) | Comparison of mean biomarker level change between intervention and control groups. Units: u/L |
| Death Within 30 Days | Baseline through 30 days | Comparison of mortality between intervention and control groups |
| Major Adverse Cardiac Events | From date of enrollment through date of discharge or death, whichever comes first (up to 100 days) | Compare frequency of major adverse cardiac events (MACE) between intervention and control groups |
| Patient-reported Functional Status at 1 Month | 1 month post-discharge | 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 |
| Patient-reported Functional Status at 3 Months | 3 months post-discharge | 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 |
| Patient-reported Functional Status at 6 Months | 6 months post-discharge | 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 |
| Patient-reported Functional Status at 12 Months | 12 months post-discharge | 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 |
| Need for ECMO | From date of enrollment through date of discharge or death, whichever comes first (up to 100 days) | Comparison of ECMO incidence between intervention and control groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention 10ml intravenous hAF QD for 5 consecutive days
Human Amniotic Fluid: Patients will receive 10ml intravenous hAF each day for 5 consecutive days. | 23 |
| Standard of Care 10 mL normal saline QD for 5 days | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Intervention | Standard of Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 16 Participants | 33 Participants |
| Age, Continuous | 56.8 years STANDARD_DEVIATION 16.09 | 58.8 years STANDARD_DEVIATION 12.8 | 57.8 years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 19 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 15 Participants | 19 Participants | 34 Participants |
| Region of Enrollment United States | 23 Participants | 24 Participants | 47 Participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 23 | 0 / 24 |
| other Total, other adverse events | 13 / 23 | 11 / 24 |
| serious Total, serious adverse events | 5 / 23 | 2 / 24 |
Outcome results
Primary
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
Time frame: Baseline through post-treatment (6 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | C-reactive Protein | -3.6 mg/dL | Standard Deviation 8.58 |
| Standard of Care | C-reactive Protein | -5.5 mg/dL | Standard Deviation 5.42 |
Other Pre-specified
Any ICU Admission
Comparison of ICU admissions between intervention and control groups
Time frame: Baseline through 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Any ICU Admission | 8 Participants |
| Standard of Care | Any ICU Admission | 4 Participants |
Other Pre-specified
Biomarker Levels (D-dimer)
Comparison of mean biomarker level change between intervention and control groups. Units: mg/mL
Time frame: Baseline through post-treatment (6 days)
Population: Data is missing for patients who did not have Day 6 labs drawn.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Biomarker Levels (D-dimer) | -0.3 mg/mL | Standard Deviation 1.77 |
| Standard of Care | Biomarker Levels (D-dimer) | 1.8 mg/mL | Standard Deviation 11.8 |
Other Pre-specified
Biomarker Levels (Interleukin-6)
Comparison of mean biomarker level change between intervention and control groups. Units: pg/mL
Time frame: Baseline through post-treatment (6 days)
Population: Data is missing for patients who did not have Day 6 labs drawn.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Biomarker Levels (Interleukin-6) | 9.4 pg/mL | Standard Deviation 24.11 |
| Standard of Care | Biomarker Levels (Interleukin-6) | 32 pg/mL | Standard Deviation 107.77 |
Other Pre-specified
Biomarker Levels (Lactate Dehydrogenase)
Comparison of mean biomarker level change between intervention and control groups. Units: u/L
Time frame: Baseline through post-treatment (6 days)
Population: Data is missing for patients who did not have Day 6 labs drawn.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Biomarker Levels (Lactate Dehydrogenase) | -87.3 U/L | Standard Deviation 124.8 |
| Standard of Care | Biomarker Levels (Lactate Dehydrogenase) | -54.4 U/L | Standard Deviation 80.8 |
Other Pre-specified
Death Within 30 Days
Comparison of mortality between intervention and control groups
Time frame: Baseline through 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Death Within 30 Days | 2 Participants |
| Standard of Care | Death Within 30 Days | 0 Participants |
Other Pre-specified
Hospital Length of Stay
Comparison of days spent in hospital between intervention and control groups
Time frame: From date of hospital admission through date of discharge or death, whichever comes first (up to 100 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Hospital Length of Stay | 7.4 days | Standard Deviation 6.69 |
| Standard of Care | Hospital Length of Stay | 7 days | Standard Deviation 6.04 |
Other Pre-specified
Major Adverse Cardiac Events
Compare frequency of major adverse cardiac events (MACE) between intervention and control groups
Time frame: From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Major Adverse Cardiac Events | 1 Participants |
| Standard of Care | Major Adverse Cardiac Events | 0 Participants |
Other Pre-specified
Need for ECMO
Comparison of ECMO incidence between intervention and control groups
Time frame: From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Need for ECMO | 0 Participants |
| Standard of Care | Need for ECMO | 0 Participants |
Other Pre-specified
Need for Invasive Mechanical Ventilation
Comparison of mechanical ventilation incidence between intervention and control groups
Time frame: From date of enrollment through date of discharge or death, whichever comes first (up to 100 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Need for Invasive Mechanical Ventilation | 4 Participants |
| Standard of Care | Need for Invasive Mechanical Ventilation | 1 Participants |
Other Pre-specified
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
Time frame: 12 months post-discharge
Population: Data missing from patients who did not complete Month 12 surveys.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Patient-reported Functional Status at 12 Months | 51.8 t-score | Standard Deviation 9.66 |
| Standard of Care | Patient-reported Functional Status at 12 Months | 42.9 t-score | Standard Deviation 10.9 |
| Month 1 PROMIS Dyspnea Severity: Intervention | Patient-reported Functional Status at 12 Months | 31.8 t-score | Standard Deviation 8.62 |
| Month 1 PROMIS Dyspnea Severity: Control | Patient-reported Functional Status at 12 Months | 41.6 t-score | Standard Deviation 12.3 |
| Month 1 PROMIS Sleep Disturbance: Intervention | Patient-reported Functional Status at 12 Months | 47.1 t-score | Standard Deviation 12.6 |
| Month 1 PROMIS Sleep Disturbance: Control | Patient-reported Functional Status at 12 Months | 49.9 t-score | Standard Deviation 7.64 |
| Month 1 PROMIS Anxiety: Intervention | Patient-reported Functional Status at 12 Months | 42.3 t-score | Standard Deviation 5.73 |
| Month 1 PROMIS Anxiety: Control | Patient-reported Functional Status at 12 Months | 47.4 t-score | Standard Deviation 9.38 |
Other Pre-specified
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
Time frame: 1 month post-discharge
Population: Data is missing for patients who did not complete Month 1 surveys.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Patient-reported Functional Status at 1 Month | 39.8 t-score | Standard Deviation 8.54 |
| Standard of Care | Patient-reported Functional Status at 1 Month | 41.5 t-score | Standard Deviation 9.1 |
| Month 1 PROMIS Dyspnea Severity: Intervention | Patient-reported Functional Status at 1 Month | 41.6 t-score | Standard Deviation 9.36 |
| Month 1 PROMIS Dyspnea Severity: Control | Patient-reported Functional Status at 1 Month | 43.0 t-score | Standard Deviation 9.71 |
| Month 1 PROMIS Sleep Disturbance: Intervention | Patient-reported Functional Status at 1 Month | 47.8 t-score | Standard Deviation 9.81 |
| Month 1 PROMIS Sleep Disturbance: Control | Patient-reported Functional Status at 1 Month | 52.2 t-score | Standard Deviation 4.98 |
| Month 1 PROMIS Anxiety: Intervention | Patient-reported Functional Status at 1 Month | 47.0 t-score | Standard Deviation 9.18 |
| Month 1 PROMIS Anxiety: Control | Patient-reported Functional Status at 1 Month | 51.1 t-score | Standard Deviation 47 |
Other Pre-specified
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
Time frame: 3 months post-discharge
Population: Data is missing for patients who did not complete Month 3 surveys.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Patient-reported Functional Status at 3 Months | 42.9 t-score | Standard Deviation 7.3 |
| Standard of Care | Patient-reported Functional Status at 3 Months | 43.9 t-score | Standard Deviation 10.4 |
| Month 1 PROMIS Dyspnea Severity: Intervention | Patient-reported Functional Status at 3 Months | 37.2 t-score | Standard Deviation 10.3 |
| Month 1 PROMIS Dyspnea Severity: Control | Patient-reported Functional Status at 3 Months | 41.5 t-score | Standard Deviation 14.8 |
| Month 1 PROMIS Sleep Disturbance: Intervention | Patient-reported Functional Status at 3 Months | 45.4 t-score | Standard Deviation 10.8 |
| Month 1 PROMIS Sleep Disturbance: Control | Patient-reported Functional Status at 3 Months | 50.5 t-score | Standard Deviation 8.55 |
| Month 1 PROMIS Anxiety: Intervention | Patient-reported Functional Status at 3 Months | 43.6 t-score | Standard Deviation 6.87 |
| Month 1 PROMIS Anxiety: Control | Patient-reported Functional Status at 3 Months | 50.9 t-score | Standard Deviation 7.84 |
Other Pre-specified
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
Time frame: 6 months post-discharge
Population: Data is missing for patients who did not complete Month 6 surveys.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Patient-reported Functional Status at 6 Months | 45.0 t-score | Standard Deviation 6.3 |
| Standard of Care | Patient-reported Functional Status at 6 Months | 44.3 t-score | Standard Deviation 11.6 |
| Month 1 PROMIS Dyspnea Severity: Intervention | Patient-reported Functional Status at 6 Months | 37.6 t-score | Standard Deviation 9.21 |
| Month 1 PROMIS Dyspnea Severity: Control | Patient-reported Functional Status at 6 Months | 37.2 t-score | Standard Deviation 10.8 |
| Month 1 PROMIS Sleep Disturbance: Intervention | Patient-reported Functional Status at 6 Months | 48.0 t-score | Standard Deviation 10.2 |
| Month 1 PROMIS Sleep Disturbance: Control | Patient-reported Functional Status at 6 Months | 47.1 t-score | Standard Deviation 6.84 |
| Month 1 PROMIS Anxiety: Intervention | Patient-reported Functional Status at 6 Months | 39.4 t-score | Standard Deviation 3.23 |
| Month 1 PROMIS Anxiety: Control | Patient-reported Functional Status at 6 Months | 51.7 t-score | Standard Deviation 8.46 |