Back to resultsMesenchymal Stromal Cells for the Treatment of Patients With COVID-19.
Primary Purpose
COVID-19 Pneumonia, COVID-19
Status
Withdrawn
Phase
Phase 1
Locations
Brazil
Study Type
Interventional
Intervention
Mesenchymal stem cell
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 Pneumonia
Eligibility Criteria
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.
Sites / Locations
- Paulo Roberto Slud Brofman
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment
Placebo
Arm Description
Patient: Intravenous infusion of single-dose of Mesenchymal stem cells (MSCs)
Intravenous infusion of single-dose of Ringer's lactate, albumin and heparin solution
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Pulmonary function test to evaluate the improvement of respiratory function
Evaluation of lung function.
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.
6-minute walk to evaluate the improvement of respiratory function
Distance covered by the patient in a period of 6 minutes.
Decrease on days of non-invasive mechanical ventilation
Analysis of ventilatory parameters and arterial blood gas analysis.
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.
Blood count to evaluate the improvement of laboratory parameters
Red blood cells, hemoglobin, hematocrit, total leukocytes, basophil, eosinophil, neutrophil, lymphocytes, monocytes, platelets.
Viral load to evaluate the improvement of laboratory parameters
Expression of the RpRd gene.
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) α, monocyte chemoattractant protein-1 (MCP1/CCL2) and macrophage inflammatory protein 1-alpha (MIP1a/CCL3).
Decrease in hospital stay
Evaluation of hospitalization days.
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.
Reduction in the percentage of intubated patients
Clinical evaluation of patients.
Decrease in mortality
Evaluation of the number of patients who died during the study.
Full Information
NCT ID
NCT05433298
First Posted
May 19, 2022
Last Updated
May 4, 2023
Sponsor
Paulo Brofman
Collaborators
Conselho Nacional de Desenvolvimento Científico e Tecnológico
1. Study Identification
Unique Protocol Identification Number
NCT05433298
Brief Title
Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19.
Official Title
Multicenter Phase I/IIa Study of Mesenchymal Stromal Cells for the Treatment of Patients With SARS-CoV-2 Pneumonia.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Withdrawn
Why Stopped
No patient could be included because there was a decrease in the number of patients with complications due to COVID-19. Also, a Brazilian government agency granted this clinical trial, and the project execution period ended in March 2023.
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
November 26, 2022 (Anticipated)
Study Completion Date
March 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Paulo Brofman
Collaborators
Conselho Nacional de Desenvolvimento Científico e Tecnológico
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia, COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Patient: Intravenous infusion of single-dose of Mesenchymal stem cells (MSCs)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous infusion of single-dose of Ringer's lactate, albumin and heparin solution
Intervention Type
Biological
Intervention Name(s)
Mesenchymal stem cell
Intervention Description
Administration of advanced cell product
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Ringer's lactate, albumin and heparin solution
Primary Outcome Measure Information:
Title
Safety of intravenously infused UCT-MSC suspension
Description
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.
Time Frame
After first cell infusion until the end of study. The clinical follow-up of patients will be one year after the transplant.
Secondary Outcome Measure Information:
Title
Pulmonary function test to evaluate the improvement of respiratory function
Description
Evaluation of lung function.
Time Frame
Pre-infusion, on days 5 and 28, 3 and 6 months.
Title
Radiography to evaluate the improvement of respiratory function
Description
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.
Time Frame
Pre-infusion, on days 5 and 28, 3 and 6 months.
Title
6-minute walk to evaluate the improvement of respiratory function
Description
Distance covered by the patient in a period of 6 minutes.
Time Frame
Pre-infusion, on days 5 and 28, 3 and 6 months.
Title
Decrease on days of non-invasive mechanical ventilation
Description
Analysis of ventilatory parameters and arterial blood gas analysis.
Time Frame
Six hours after infusion, days 1, 5 and 28, 3 and 6 months.
Title
Biochemical tests to evaluate the improvement of laboratory parameters
Description
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.
Time Frame
Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Title
Blood count to evaluate the improvement of laboratory parameters
Description
Red blood cells, hemoglobin, hematocrit, total leukocytes, basophil, eosinophil, neutrophil, lymphocytes, monocytes, platelets.
Time Frame
Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Title
Viral load to evaluate the improvement of laboratory parameters
Description
Expression of the RpRd gene.
Time Frame
Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Title
Cytokine dosage to evaluate inflammatory parameters
Description
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).
Time Frame
Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
Title
Decrease in hospital stay
Description
Evaluation of hospitalization days.
Time Frame
From admission to discharge, or a maximum of 6 months.
Title
Computed tomography score to evaluate the improvement of pulmonary function
Description
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.
Time Frame
Pre-infusion, on days 5 and 28, 3 and 6 months.
Title
Reduction in the percentage of intubated patients
Description
Clinical evaluation of patients.
Time Frame
After first cell infusion until six months after the transplant.
Title
Decrease in mortality
Description
Evaluation of the number of patients who died during the study.
Time Frame
After first cell infusion until the end of study. The clinical follow-up of patients will be six months after the transplant.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paulo R Brofman, phD
Organizational Affiliation
Pontifícia Universidade Católica do Paraná
Official's Role
Principal Investigator
Facility Information:
Facility Name
Paulo Roberto Slud Brofman
City
Curitiba
State/Province
Paraná
ZIP/Postal Code
80215200
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35313959
Citation
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 improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial. Stem Cell Res Ther. 2022 Mar 21;13(1):122. doi: 10.1186/s13287-022-02796-1.
Results Reference
result
PubMed Identifier
34074163
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 Mesenchymal Stromal Cells in the Treatment of Severe Covid-19: Case Report. Cell Transplant. 2021 Jan-Dec;30:9636897211021008. doi: 10.1177/09636897211021008.
Results Reference
result
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/35313959/
Description
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.
URL
https://pubmed.ncbi.nlm.nih.gov/34074163/
Description
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.
Learn more about this trial
Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19.
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