Clinical trial NCT04355728: Use of UC-MSCs for COVID-19 Patients
Official title: Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Corona Virus Infection
ARDS
ARDS, Human
Acute Respiratory Distress Syndrome
COVID-19
Keywords: COVID-19
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The trial has two groups, each with 12 subjects (n=24). All eligible subjects will be randomized to either the treatment group or standard of care, and randomization will be stratified by ARDS severity.
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).


Eligibility criteria: Inclusion Criteria:

Patients \>/= 18 years old diagnosed with COVID-19 (as evaluated by PCR test confirming infection with SARS-CoV-2) will be eligible for inclusion if they meet all of the below criteria. Inclusion criteria must all be present within a 24-hour time period at the time of enrollment:

1. Patient currently hospitalized
2. Aged ≥ 18 years
3. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
4. Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
5. PaO2/FiO2 ratio \< 300 mmHg
6. Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
7. Hypoxemia requiring an increase in the fraction of inspired oxygen (FiO2) of ≥ 20% AND an increase in positive end-expiratory airway pressure (PEEP) level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95%, or requirement for escalation from oxygen therapy to invasive mechanical ventilation

Exclusion Criteria:

1. PaO2/FiO2 ≥ 300 at the time of enrollment
2. A previous MSC infusion not related to this trial
3. History of Pulmonary Hypertension (WHO Class III/IV)
4. History of left atrial hypertension or decompensated left heart failure.
5. Pregnant or lactating patient
6. Unstable arrhythmia
7. Patients with previous lung transplant
8. Patients currently receiving chronic dialysis
9. Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
10. Presence of any active malignancy (except non-melanoma skin cancer)
11. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
12. Moderate to severe liver disease (AST and ALT \>5 X ULN)
13. Severe chronic respiratory disease with a PaCO2 \> 50 mm Hg or the use of home oxygen
14. Baseline QT prolongation
15. Moribund patient not expected to survive \> 24 hours

Primary outcomes:
measure: Number of Participants With Pre-Specified Infusion Associated Adverse Events
timeFrame: 6 and 24 hours
measure: Number of Subjects With Serious Adverse Events by 31 Days After First Infusion
timeFrame: 31 days
measure: Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90
timeFrame: 90 days
measure: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 90 days
measure: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity
timeFrame: 90 days
measure: Subjects With Adverse Events and Serious Adverse Events by Severity
timeFrame: 90 days
measure: Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment
timeFrame: 90 days
measure: Subjects With Adverse Events by Relatedness to Treatment
timeFrame: 90 days
Secondary outcomes:
measure: Survival at 31 Days Post First Infusion
timeFrame: 31 Days
measure: Survival at 60 Days Post First Infusion
timeFrame: 60 days
measure: Time to Recovery
timeFrame: 31 days
measure: Ventilator-Free Days Throughout 28 Days Post Second Infusion
timeFrame: 28 days post second infusion
measure: Ventilator-Free Days Throughout 90 Days
timeFrame: 90 days or hospital discharge, whichever is earlier
measure: Respiratory Rate and Oxygenation Index (ROX Index)
timeFrame: day 6
measure: Oxygenation Index (OI)
timeFrame: day 6
measure: Positive End-Expiratory Pressure (PEEP) and Plateau Pressure (Pplat)
timeFrame: day 6
measure: Sequential Organ Failure Assessment (SOFA) Scores
timeFrame: Day 6
measure: Smell Identification Test (SIT) Scores
timeFrame: 90 days
measure: White Blood Cell Count (WBC)
timeFrame: day 6
measure: Platelets Count
timeFrame: day 6
measure: Hemogoblin
timeFrame: day 6
measure: Hematocrit
timeFrame: day 6
measure: Neutrophils
timeFrame: day 6
measure: Lymphocytes
timeFrame: day 6
measure: Glomerular Filtration Rate
timeFrame: day 6
measure: Total Protein
timeFrame: Day 6
measure: Sodium
timeFrame: day 6
measure: Potassium
timeFrame: day 6
measure: Creatinine
timeFrame: day 6
measure: Glucose
timeFrame: day 6
measure: Albumin
timeFrame: day 6
measure: Alkaline Phosphatase
timeFrame: day 6
measure: Alanine Aminotransferase or Serum Glutamate-pyruvate Transaminase (ALT or SGPT)
timeFrame: day 6
measure: Aspartate Aminotransferase or Serum Glutamic Oxaloacetic Transaminase (AST or SGOT)
timeFrame: day 6
measure: Total Bilirubin
timeFrame: day 6
measure: Blood Urea Nitrogen (BUN)
timeFrame: day 6
measure: Calcium
timeFrame: day 6
measure: Chloride
timeFrame: day 6
measure: Carbon Dioxide (CO2)
timeFrame: day 6
measure: C-Reactive Protein Levels
timeFrame: day 6
measure: Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio
timeFrame: day 6
measure: D-dimer Levels
timeFrame: day 6
measure: 25-Hydroxy Vitamin D Levels
timeFrame: day 6
measure: Tumor Necrosis Factor-alpha (TNFα)
timeFrame: day 6
measure: Tumor Necrosis Factor-beta (TNFβ)
timeFrame: day 6
measure: Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)
timeFrame: day 6
measure: Viral Load by SARS-CoV-2 RT-PCR
timeFrame: day 6
measure: Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 3 Post First Infusion
timeFrame: day 3 post first infusion
measure: Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 6 Post First Infusion
timeFrame: day 6
measure: Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 14 Post First Infusion
timeFrame: day 14
measure: Number of Participants With Positive, Negative, or Borderline Serology Testing for SARS-CoV-2 IgM/IgG
timeFrame: day 14 post first infusion
Other outcomes:
Locations:
city: Miami
country: United States
facility: Diabetes Research Institute, University of Miami Miller School of Medicine
state: Florida
Study officials:
affiliation: University of Miami
name: Camillo Ricordi, MD
role: PRINCIPAL_INVESTIGATOR
References: