Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19.

COVID-19 Clinical Trial

Official title:

Multicenter Phase I/IIa Study of Mesenchymal Stromal Cells for the Treatment of Patients With SARS-CoV-2 Pneumonia.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05433298
• Other study ID #: MSC SARS-CoV-2
• Secondary ID: U1111-1267-12003
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: May 1, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: May 2023
• Source: Pontifícia Universidade Católica do Paraná
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is evaluate the feasibility, safety and potential efficacy of an advanced cell therapy product for the treatment of patients with SARS-CoV-2 pneumonia.

Description:

Forty patients with COVID-19 will receive an intravenous infusion of one dose of 1.000.000 umbilical cord mesenchymal cells per kilo of the patient. Twenty patients will receive a placebo (Ringer's lactate solution, albumin and heparin). Conventional treatment will be performed together with the infusion of cells, during the study period. The evaluation times will be at pre-infusion, 6 and 24 hours, days 5 and 28, 3 and 6 months. The patient exams performed: serology, biochemistry, blood count and blood gas analysis, metabolomics/proteomics, antibody evaluation, electrocardiogram, CT-scan and X-ray, cytokines, viral load, cytometry, and clinical evaluation. The patients will be evaluated all the time, during hospitalization period, to assess adverse events.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 31, 2023
• Est. primary completion date: November 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Both sexes;
• aged 18 to 79 years old;
• hospitalized patients;
• radiological diagnosis of viral pneumonia;
• virological diagnosis of SARS-CoV-2 infection;
• with noninvasive ventilatory support;
• C-reactive protein and ferritin above the reference value considered normal;
• assent confirmed to participate in the study.

Exclusion Criteria:

• Contraindications for use of corticosteroids;
• immunosuppressive, cytotoxic and antiviral treatment, experimental medications and chronic corticosteroid use;
• morbid obesity (BMI> 35);
• multiple organ dysfunction syndrome;
• pre-malignant neoplastic conditions with life expectancy lower than 1 year old;
• pre-existing chronic illnesses like chronic dialysis kidney disease, chronic liver disease, congestive heart failure Class IV; pulmonary hypertension (WHO Class III/IV);
• pre-existing or current thromboembolic pathology;
• transplanted patients;
• pre-existing severe allergic reaction;
• history of HIV and tuberculosis;
• enrollment in another clinical trial;
• pregnancy or breastfeeding.

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

Biological:
• Mesenchymal stem cell
Administration of advanced cell product

Other:
• Placebo
Ringer's lactate, albumin and heparin solution

Locations

Country	Name	City	State
Brazil	Paulo Roberto Slud Brofman	Curitiba	Paraná

Sponsors (2)

Lead Sponsor	Collaborator
Paulo Brofman	Conselho Nacional de Desenvolvimento Científico e Tecnológico

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

Rebelatto CLK, Senegaglia AC, Franck CL, Daga DR, Shigunov P, Stimamiglio MA, Marsaro DB, Schaidt B, Micosky A, de Azambuja AP, Leitao CA, Petterle RR, Jamur VR, Vaz IM, Mallmann AP, Carraro Junior H, Ditzel E, Brofman PRS, Correa A. Safety and long-term — View Citation

Senegaglia AC, Rebelatto CLK, Franck CL, Lima JS, Boldrini-Leite LM, Daga DR, Leitao CA, Shigunov P, de Azambuja AP, Bana E, Marsaro DB, Schaidt B, Micosky A, Jamur VR, Schluga Y, Vaz IM, Ribeiro LL, Correa A, Brofman EPRS. Combined Use of Tocilizumab and — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of intravenously infused UCT-MSC suspension	The primary expected outcome is the safety and tolerability of using intravenously infused UTC-MSC suspension in patients with pneumonia caused by SARS-CoV-2. This outcome will be evaluated by recording adverse events that must be reported throughout the study period.	After first cell infusion until the end of study. The clinical follow-up of patients will be one year after the transplant.
Secondary	Pulmonary function test to evaluate the improvement of respiratory function	Evaluation of lung function.	Pre-infusion, on days 5 and 28, 3 and 6 months.
Secondary	Radiography to evaluate the improvement of respiratory function	Evaluation of pulmonary function using breathing chest radiography. Assessment of peripheral opacities, interstitial and airspace opacities, diffuse airspace opacities, interstitial opacities, lobar consolidation, atelectasis, cavities, pulmonary cysts, and emphysema.	Pre-infusion, on days 5 and 28, 3 and 6 months.
Secondary	6-minute walk to evaluate the improvement of respiratory function	Distance covered by the patient in a period of 6 minutes.	Pre-infusion, on days 5 and 28, 3 and 6 months.
Secondary	Decrease on days of non-invasive mechanical ventilation	Analysis of ventilatory parameters and arterial blood gas analysis.	Six hours after infusion, days 1, 5 and 28, 3 and 6 months.
Secondary	Biochemical tests to evaluate the improvement of laboratory parameters	D-dimer, C-reactive protein, erythrocyte sedimentation rate, ferritin, creatine, urea, saline, potassium, bilirubin, total protein and fractions, albumin, globulin, oxalacetic transaminase, pyruvic transaminase, lactate dehydrogenase, creatine phosphokinase, troponin I, coagulogram.	Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Secondary	Blood count to evaluate the improvement of laboratory parameters	Red blood cells, hemoglobin, hematocrit, total leukocytes, basophil, eosinophil, neutrophil, lymphocytes, monocytes, platelets.	Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Secondary	Viral load to evaluate the improvement of laboratory parameters	Expression of the RpRd gene.	Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Secondary	Cytokine dosage to evaluate inflammatory parameters	Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL) -2, IL-6, IL-7, IL-8, tumor necrosis factor (TNF) a, monocyte chemoattractant protein-1 (MCP1/CCL2) and macrophage inflammatory protein 1-alpha (MIP1a/CCL3).	Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Secondary	Decrease in hospital stay	Evaluation of hospitalization days.	From admission to discharge, or a maximum of 6 months.
Secondary	Computed tomography score to evaluate the improvement of pulmonary function	Chest computed tomography evaluation will analyze the following characteristics: ground glass opacities, linear opacities, consolidation, interlobular septal thickening, crazy-paving pattern, subpleural lines, bronchial wall thickening, lymph node enlargement and pleural effusion. Lesions will quantify by assigning a score to all abnormal areas involved. Each lobe will assigned a score of 0 (0% involvement), 1 (1-25% involvement), 2 (26-50% involvement), 3 (51-75% involvement) or 4 (76%-100% involvement). The total score will be the sum of all lobes, ranging from 0 to 25.	Pre-infusion, on days 5 and 28, 3 and 6 months.
Secondary	Reduction in the percentage of intubated patients	Clinical evaluation of patients.	After first cell infusion until six months after the transplant.
Secondary	Decrease in mortality	Evaluation of the number of patients who died during the study.	After first cell infusion until the end of study. The clinical follow-up of patients will be six months after the transplant.

External Links

•   The combination of tocilizumab and UC-MSC proved to be safe, with no adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2.
•   UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients.