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Treatment of Severe COVID-19 Pneumonia With Allogeneic Mesenchymal Stem Cells

Double Blind, Placebo-controlled, Phase I/II Clinical Trial to Evaluate Safety and Efficacy of Allogeneic Mesenchymal Stem/Stromal Cells MSV-allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (MSV-COVID)

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04361942
Acronym
MSV-COVID
Enrollment
24
Registered
2020-04-24
Start date
2020-05-01
Completion date
2021-10-28
Last updated
2024-02-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19 Pneumonia

Keywords

COVID-19, Mesenchymal Stromal Cells, Mesenchymal Stem Cells, MSV

Brief summary

Novel coronavirus disease COVID-19, produced by SARS-CoV-2, has become a health emergency around the world. Since first patients were detected in Wuhan (China), in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem/stromal cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the double-blind, placebo-controlled, randomized, phase I/II clinical trial to evaluate safety and efficacy of allogeneic MSCs for treatment of severe COVID-19 pneumonia.

Detailed description

Novel coronavirus disease COVID-19, produced by SARS-CoV-2, has spread quickly from Wuhan (China) to worldwide. On April 15, 2020, the World Health Organization (WHO) has reported 1.914.916 confirmed cases and 123.010 deaths globally, being a severe threat to public health. Some patients develop overwhelming lung inflammation and acute respiratory failure. Several reports demonstrated that SARS-CoV-2 specifically recognize the angiotensin I converting ezyme 2 receptor (ACE2) and ACE2-positive cells are infected by the virus. ACE2 receptor is widely present on the human cells surface such as alveolar type II cells and capillary endothelium, among others. SARS-CoV-2 infects cells and stimulates a terrible cytokine storm in the lung followed by edema, dysfunction of the air exchange and acute respiratory distress which may lead to death. Further, once SARS-CoV-2 enters in blood circulation, it can easily spread to some systems and organs, causing significant damage. Under these circumstances, it is reasonable to believe that the inhibition of inflammatory response is the key to treat COVID-19 pneumonia. Mesenchymal stem/stromal cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. Some studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 viruses, reducing proinflammatory cytokines and inflammatory cells into the lungs. These immunomodulatory properties of MSCs support performance of the placebo-controlled, double-blind (neither the participant nor the investigator will know if active drug or placebo is assigned), randomized (assigned by chance), phase I/II clinical trial in which subjects with severe COVID-19 pneumonia will receive either MSCs (1 million cells/kg) or placebo by intravenous injection. The administration of cells will be done only once.

Interventions

Intravenous injection of 1 million MSCs (MSV cells)/Kg suspended in 100 ml physiological saline solution.

OTHERPlacebo

Intravenous injection of 100 ml physiological saline solution containing no cells

Sponsors

Citospin
CollaboratorINDUSTRY
University of Valladolid
CollaboratorOTHER
Castilla-León Health Service
CollaboratorOTHER
Hospital del Rio Hortega
CollaboratorOTHER
Instituto de Salud Carlos III
CollaboratorOTHER_GOV
Red de Terapia Celular
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Masking description

Both experimental and placebo groups will receive a similar endovenous injection with either cells or placebo, respectively. Blind to participant, investigator and care providers.

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

1. Women or men of ≥ 18 years of age 2. SARS-CoV-2 infection confirmed by molecular testing. 3. Admitted to the Intensive Care Unit with pneumonia by COVID-19 infection and intubated in the last 48 hours, that meet at least one of these criteria: 1. Respiratory distress. 2. Respiratory rate (RR) ≥ 30 rpm. 3. Basal oxygen saturation at rest ≤ 93%. 4. Arterial partial pressure of oxygen (PaO2) / inspiratory fraction of oxygen (FiO2) ≤ 300 mmHg. 4. Consent of the patient or his/her legal representative for participation in the study.

Exclusion criteria

1. Active tumor disease. 2. Pregnancy. 3. Participation in another active clinical trial. 4. Any circumstance that in the researcher's opinion justifies the patient's non-participation in the trial. 5. Not consent to participation.

Design outcomes

Primary

MeasureTime frameDescription
Proportion of patients in whom removal of invasive mechanical ventilation (IMV) has been achieved0-7 daysIndex of therapy success to preserve Intensive Care Unit (ICU) space.
Overall survival0-28 daysTo measure global success

Secondary

MeasureTime frameDescription
Complete radiological response0-28 daysProportion of patients over time that show lung images free from opacities or condensations
Complete clinical response0-Event/Loss to follow-upProportion of patients over time that meet the weaning criteria, defined as (i) PaO2/FiO2 ≥ 200 mmHg, (ii) mechanical ventilation with PEEP ≤ 8 (only if BMI\<30), (iii) mechanical ventilation with FiO2 ≤ 50% and (iv) no continuous relaxation (cisatracurium) or prone maneuvers in the last 24 hours.
Radiological improvement of pulmonary images0-5 daysChange in the proportion of lung sections affected by opacities/condensations in chest X-ray images
Removal of invasive mechanical ventilation (IMV)0-28 daysProportion of patients over time that reach the event (removal of IMV)

Other

MeasureTime frameDescription
Levels of circulating immune cells0-7 daysB cells, NK cells, T cells, CD4+ T cells, CD8+ T cells
Levels of cytokines and other inflammatory markers in peripheral blood0-7 daysInterleukin-6 (IL-6), D dimer, C reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin.
Levels of renal and liver function markers0-7 daysUrea, creatinine, gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT).

Countries

Spain

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026