Safety and Efficacy of Intravenous Wharton's Jelly Derived Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Due to COVID 19

BioXcellerator

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Acute Respiratory Distress Syndrome

Treatments: Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy); Drug: Wharton's jelly derived Mesenchymal stem cells.

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04390152

BIOXSOMCOV001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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6 participants in 2 patient groups

Mesenchymal stem cell

Experimental group

Description:

WJ MSC 50\*10e6, two doses plus standard treatment with hydroxychloroquine + Lopinavir/Ritonavir or Azithromycin and ventilation support.

Treatment:

Drug: Wharton's jelly derived Mesenchymal stem cells.

Control group

Active Comparator group

Description:

Hydroxychloroquine, lopinavir/ritonavir and ventilation support plus placebo

Treatment:

Drug: Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy)