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

Phase 1
Withdrawn
Conditions
COVID-19 Pneumonia
COVID-19
Interventions
Registration Number
NCT05433298
Lead Sponsor
Paulo Brofman
Brief 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.

Detailed 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 & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboIntravenous infusion of single-dose of Ringer's lactate, albumin and heparin solution
TreatmentMesenchymal stem cellPatient: Intravenous infusion of single-dose of Mesenchymal stem cells (MSCs)
Primary Outcome Measures
NameTimeMethod
Safety of intravenously infused UCT-MSC suspensionAfter first cell infusion until the end of study. The clinical follow-up of patients will be one year after the transplant.

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.

Secondary Outcome Measures
NameTimeMethod
Pulmonary function test to evaluate the improvement of respiratory functionPre-infusion, on days 5 and 28, 3 and 6 months.

Evaluation of lung function.

Radiography to evaluate the improvement of respiratory functionPre-infusion, on days 5 and 28, 3 and 6 months.

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.

6-minute walk to evaluate the improvement of respiratory functionPre-infusion, on days 5 and 28, 3 and 6 months.

Distance covered by the patient in a period of 6 minutes.

Decrease on days of non-invasive mechanical ventilationSix hours after infusion, days 1, 5 and 28, 3 and 6 months.

Analysis of ventilatory parameters and arterial blood gas analysis.

Biochemical tests to evaluate the improvement of laboratory parametersPre-infusion, on days 1, 5 and 28, 3 and 6 months.

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.

Blood count to evaluate the improvement of laboratory parametersPre-infusion, on days 1, 5 and 28, 3 and 6 months.

Red blood cells, hemoglobin, hematocrit, total leukocytes, basophil, eosinophil, neutrophil, lymphocytes, monocytes, platelets.

Viral load to evaluate the improvement of laboratory parametersPre-infusion, on days 1, 5 and 28, 3 and 6 months.

Expression of the RpRd gene.

Cytokine dosage to evaluate inflammatory parametersPre-infusion, on days 1, 5 and 28, 3 and 6 months.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL) -2, IL-6, IL-7, IL-8, tumor necrosis factor (TNF) α, monocyte chemoattractant protein-1 (MCP1/CCL2) and macrophage inflammatory protein 1-alpha (MIP1a/CCL3).

Decrease in hospital stayFrom admission to discharge, or a maximum of 6 months.

Evaluation of hospitalization days.

Computed tomography score to evaluate the improvement of pulmonary functionPre-infusion, on days 5 and 28, 3 and 6 months.

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.

Reduction in the percentage of intubated patientsAfter first cell infusion until six months after the transplant.

Clinical evaluation of patients.

Decrease in mortalityAfter first cell infusion until the end of study. The clinical follow-up of patients will be six months after the transplant.

Evaluation of the number of patients who died during the study.

Trial Locations

Locations (1)

Paulo Roberto Slud Brofman

🇧🇷

Curitiba, Paraná, Brazil

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