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.
Drug: Wharton's jelly derived Mesenchymal stem cells.
IV Wharton's jelly derived Mesenchymal stem cells, two doses
Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)
Standard therapy as per hospital protocol, hydroxychloroquine 400mg + Lopinavir/Ritonavir 400/100 or azithromycin 500mg and Placebo
Inclusion Criteria:
- SARS-CoV-2 positive Real Time - Polymerase Chain Reaction
- Moderate to severe Acute respiratory distress syndrome according to Murray
classification.
- PaO2/FiO2 less than 200 mmHg.
- Within 36 hours of orotracheal intubation.
- Absence of response with previous standard therapy.
- Willing to participate in the study expressed by patient or responsible caregiver.
- Not being in other clinical trial.
Exclusion Criteria:
- Current pregnancy.
- Cardiac rhythm abnormalities with instability.
- Acute congestive heart failure/cardiogenic shock.
- Severe comorbidities affecting mortality as defined by research group.
- Cancer history in the past 5 years.
- HIV, syphilis, hepatitis B or C.
- Concomitant use of immunosuppressive therapy with contraindication to MSC.
- Fivefold elevation of liver enzymes (ALT, AST).
- Chronic kidney disease with glomerular filtration rate below 30ml/min or dialytic
needs.
BioXcellerator
Medellin, Antioquia-CO, Colombia
Clinical Somer
Rionegro, Antioquia, Colombia
Alfredo Hernandez-Ruiz, MSc
+5745699999 - 5386
ahernandez@clinicasomer.com
Santiago Saldarriaga-Gomez, MSc
+5746041815
santiago.saldarriaga@bioxcellerator.com
Alfredo Hernandez-Ruiz, MSc, Principal Investigator
Clinica Somer