Clinical trial NCT05433298: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: COVID-19 Pneumonia
COVID-19
Lead sponsor: Pontifícia Universidade Católica do Paraná
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2022-06-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of intravenously infused UCT-MSC suspension
timeFrame: After first cell infusion until the end of study. The clinical follow-up of patients will be one year after the transplant.
Secondary outcomes:
measure: Pulmonary function test to evaluate the improvement of respiratory function
timeFrame: Pre-infusion, on days 5 and 28, 3 and 6 months.
measure: Radiography to evaluate the improvement of respiratory function
timeFrame: Pre-infusion, on days 5 and 28, 3 and 6 months.
measure: 6-minute walk to evaluate the improvement of respiratory function
timeFrame: Pre-infusion, on days 5 and 28, 3 and 6 months.
measure: Decrease on days of non-invasive mechanical ventilation
timeFrame: Six hours after infusion, days 1, 5 and 28, 3 and 6 months.
measure: Biochemical tests to evaluate the improvement of laboratory parameters
timeFrame: Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
measure: Blood count to evaluate the improvement of laboratory parameters
timeFrame: Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
measure: Viral load to evaluate the improvement of laboratory parameters
timeFrame: Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
measure: Cytokine dosage to evaluate inflammatory parameters
timeFrame: Pre-infusion, on days 1, 5 and 28, 3 and 6 months.
measure: Decrease in hospital stay
timeFrame: From admission to discharge, or a maximum of 6 months.
measure: Computed tomography score to evaluate the improvement of pulmonary function
timeFrame: Pre-infusion, on days 5 and 28, 3 and 6 months.
measure: Reduction in the percentage of intubated patients
timeFrame: After first cell infusion until six months after the transplant.
measure: Decrease in mortality
timeFrame: After first cell infusion until the end of study. The clinical follow-up of patients will be six months after the transplant.
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Paulo Roberto Slud Brofman
state: Paraná
Study officials:
affiliation: Pontifícia Universidade Católica do Paraná
name: Paulo R Brofman, phD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.