Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis. Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation. These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.
SARS-CoV-2, virus culprit of the COVID 19 that emerged in China, has become now a worldwide problem, with more than three million cases al around the world as reported by the World Health Organization. This situation has put health systems under extreme pressure, being overwhelmed be the amount of patients requiring attention. Around 5% of patients will require ICU internation, due to severe lung inflammation giving rise to Acute Respiratory Distress Syndrome (ARDS) and a cytokine storm that ultimately affects other organs. In this group, mortality can be as high as 40%. Mesenchymal stem cells (MSC) have shown great immunomodulatory effects, and are used in other inflammatory conditions as autoimmune diseases, being safe and preliminary effective in improving patients health status. They exert their effect via paracrine and autocrine pathways and have been shown to reduce IL-1, IL-6, Tumor necrosis factor alpha and increase IL-10 in COVID 19 patients. One of the greater advantages of the MSC is that they express no Major Histocompatibility Complex, reducing the risk of host immune reaction. Given their immunomodulatory effects, research in this topic showing their safety and experimental efficacy are needed, as therapies for severe patients are lacking. Patients, researchers and data analysts will be blinded, and ARDS patients will be randomly allocated in standard therapy plus MSC arm or standard therapy alone to answer these questions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
6
IV Wharton's jelly derived Mesenchymal stem cells, two doses
Standard therapy as per hospital protocol, hydroxychloroquine 400mg + Lopinavir/Ritonavir 400/100 or azithromycin 500mg and Placebo
Clinical Somer
Rionegro, Antioquia, Colombia
BioXcellerator
Medellín, Antioquia-CO, Colombia
Intergroup mortality difference with treatment
Evaluation of efficacy of WJ-MSC defined by mortality at 28 days of application.
Time frame: 28 days.
Number of patients with treatment related adverse events
Safety evaluation of WJ-MSC describing and comparing incidence, type and severity of adverse events in both groups.
Time frame: 6 months.
Difference in days of mechanical ventilation between groups
Evaluation of the effect of WJ-MSC in the time of mechanical ventilation compared between the two groups, as prolonged mechanical ventilation days are associated with higher complication risks as pneumonia, tracheostomy and death.
Time frame: From ICU admission to 180 days.
Median reduction of days of hospitalization
Evaluation of the effect of WJ-MSC in the time of hospitalization between the two groups as a measure of efficacy.
Time frame: From hospital admission to 180 days.
Median reduction of days of oxygen needs
Evaluation of the effect of WJ-MSC in the time of oxygen needs compared between the two groups as a measure of efficacy.
Time frame: From hospital admission to 180 days.
Difference between "Sequential Organ Failure Assessment" score between groups
"Sequential Organ Failure Assessment" (SOFA) score is a tool used to determine the beginning and evolution of multiorgan failure, ranging from 0 to 24, being 24 the worst scenario. It has been proven useful as an outcome predictor of mortality and ICU stay. The result is the addition of the evaluation of each organ or system. Effect of WJ-MSC in the SOFA score will be compared between the two groups.
Time frame: Baseline to 7 days
Difference between median Murray score between groups
Murray score is a tool used to classify lung injury. 0 = no lung injury, 0.1-2.5, mild to moderate lund injury, \>2.5 Acute respiratory distress syndrome. The effect of WJ-MSC in the Murray score will be compared between the two groups.
Time frame: Baseline and 7 days
Difference in APACHE II score between groups
APACHE II is a prognostic score based on 12 different items obtained in the first 24 hours of ICU admission. Its mainly used as a single measure, but some authors have used and described prediction usefulness with repeated measures. It ranges from 0 to 71 points. Higher scores are related to higher ICU mortality. The effect of WJ-MSC in the APACHE II score will compared between the two groups.
Time frame: Baseline and 7 days
Difference in lymphocyte count between groups
Evaluation of the effect of WJ-MSC in lymphocyte count measured in absolute number/mm3. These laboratory measures have been associated with COVID 19 severity.
Time frame: baseline and 21 days or discharge
Changes in C reactive protein concentration between groups
Evaluation of the effect of WJ-MSC in C reactive protein concentration between the two groups, measured in mg/dl. Highest levels have been associated with COVID 19 severity and inflammation.
Time frame: baseline and 21 days or discharge
Changes in D dimer concentration
Evaluation of the effect of WJ-MSC in D dimer between the two groups, measured in micrograms Highest levels have been associated with COVID 19 severity and thromboembolic complications.
Time frame: baseline and 21 days or discharge
Changes in ferritin concentration
Evaluation of the effect of WJ-MSC in ferritin compared between the two groups, measured in nanograms/ml. These laboratory measures have been associated with COVID 19 infection and severity.
Time frame: baseline and 21 days or discharge
Changes in lactate dehydrogenase concentration
Evaluation of the effect of WJ-MSC in LDH compared between the two groups, measured in units/liter. These laboratory measures have been associated with COVID 19 infection and severity.
Time frame: baseline and 21 days or discharge
Impact on interleukin 6 concentrations between groups.
Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation.The effect of WJ-MSC in IL-6 will be compared between the two groups. It will be measured in picograms/ml.
Time frame: Baseline and 7 days
Impact on interleukin 8 concentrations between groups.
Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 8 will be compared between the two groups. It will be measured in picograms/ml.
Time frame: Baseline and 7 days
Impact on interleukin 10 concentrations between groups.
Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in IL 10 will be compared between the two groups. It will be measured in picograms/ml.
Time frame: Baseline and 7 days
Impact on tumor necrosis factor alpha concentrations between groups.
Cytokines are biomarkers of inflammation or inflammatory activity in the human body. Changes in this profile give information about underlying process of inflammation. The effect of WJ-MSC in TNF alpha will be compared between the two groups. It will be measured in nanograms/ml.
Time frame: Baseline to 7 days.
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