Clinical trial NCT04390152: Safety and Efficacy of Intravenous Wharton's Jelly Derived Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Due to COVID 19
Official title: Safety and Efficacy of Intravenous Infusion of Wharton's Jelly Derived Mesenchymal Stem Cell Plus Standard Therapy for the Treatment of Patients With Acute Respiratory Distress Syndrome Diagnosis Due to COVID 19: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Respiratory Distress Syndrome
Keywords: coronavirus
stem cell research
mesenchymal stem cell
Lead sponsor: BioXcellerator
Sponsor class: INDUSTRY
First posted: 2020-05-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Intergroup mortality difference with treatment
timeFrame: 28 days.
Secondary outcomes:
measure: Number of patients with treatment related adverse events
timeFrame: 6 months.
measure: Difference in days of mechanical ventilation between groups
timeFrame: From ICU admission to 180 days.
measure: Median reduction of days of hospitalization
timeFrame: From hospital admission to 180 days.
measure: Median reduction of days of oxygen needs
timeFrame: From hospital admission to 180 days.
measure: Difference between "Sequential Organ Failure Assessment" score between groups
timeFrame: Baseline to 7 days
measure: Difference between median Murray score between groups
timeFrame: Baseline and 7 days
measure: Difference in APACHE II score between groups
timeFrame: Baseline and 7 days
measure: Difference in lymphocyte count between groups
timeFrame: baseline and 21 days or discharge
measure: Changes in C reactive protein concentration between groups
timeFrame: baseline and 21 days or discharge
measure: Changes in D dimer concentration
timeFrame: baseline and 21 days or discharge
measure: Changes in ferritin concentration
timeFrame: baseline and 21 days or discharge
measure: Changes in lactate dehydrogenase concentration
timeFrame: baseline and 21 days or discharge
measure: Impact on interleukin 6 concentrations between groups.
timeFrame: Baseline and 7 days
measure: Impact on interleukin 8 concentrations between groups.
timeFrame: Baseline and 7 days
measure: Impact on interleukin 10 concentrations between groups.
timeFrame: Baseline and 7 days
measure: Impact on tumor necrosis factor alpha concentrations between groups.
timeFrame: Baseline to 7 days.
Other outcomes:
measure: Changes in 6 minute walk between groups
timeFrame: 6 months
measure: Changes in Pulmonary Computed Tomography Scan between groups
timeFrame: 6 months
measure: Changes in Spirometry between groups
timeFrame: 6 months
measure: Changes in health related quality of life between groups
timeFrame: 6 months
Locations:
city: Medellin
country: Colombia
facility: BioXcellerator
state: Antioquia-CO
city: Rionegro
country: Colombia
facility: Clinical Somer
state: Antioquia
Study officials:
affiliation: Clinica Somer
name: Alfredo Hernandez-Ruiz, MSc
role: PRINCIPAL_INVESTIGATOR
References: