The purpose of this clinical trial is to evaluate the safety, tolerability and efficacy of two doses (dose A and dose B) of Standardized Conditioned Medium Obtained by Coculture of M2-macrophages and fat-derived Mesenchymal Stromal Cells (PRS CK STORM) in the modulation of the cytokine storm in participants with acute respiratory infection caused by SARS-Cov-2, influenza A, influenza B and respiratory syncytial virus (RSV) in need for oxygen therapy.
The main questions it aims to answer are:
* Are both doses of PRS CK STORM (dose A and dose B) safe as an intravenous drug to modulate inflammatory processes, such as the cytokine storm in participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV? * Are both doses of PRS CK STORM (dose A and dose B) effective as an intravenous drug to modulate SIRS-associated cytokine storm caused by SARS-Cov-2, influenza A, influenza B and RSV compared to the control group? * What are the anti-inflammatory and pro-inflammatory cytokine profiles after treatment with two different doses of PRS CK STORM in participants with SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV?
Researchers will compare both doses of PRS CK STORM with the control group to test whether the anti-inflammatory action of PRS CK STORM is safe and effective in modulating the cytokine storm for the treatment of SIRS caused by SARS-Cov-2, influenza A, influenza B and RSV. In addition, the anti-inflammatory and pro-inflammatory cytokine profiles after treatment PRS CK STORM compared to placebo group in these participants will be also studied.
Signed informed consent by the participant or legal representative prior to the initiation of any study-specific procedure.
Males and females aged ≥ 18 years old at the time of the consent.
Confirmed diagnosis of SARS-CoV-2, influenza virus A, influenza virus B or RSV pneumonia by positive RT-PCR (results of a PCR prior to screening will be valid only if the PCR has been done for all 4 viruses and in 3 days prior to the screening visit). PCR will include the analysis of SARS-Cov-2, influenza A, influenza B and RSV.
Body temperature over 38 ºC or under 36 ºC.
Failure to perform screening or baseline examinations.
Body Mass Index (BMI) more than or equal to 35.
Irreversible critical condition, as assessed by the investigator.
Active autoimmune diseases or severe immunosuppression, unless stable and controlled for at least 3 months prior to the inclusion in the study.
Sequential
Placebo comparator
Drug2 vials of saline solution 0.9% for infusion
PRS CK STORM
Drug1 vial of PRS CK STORM (dose A) and 1 vial of placebo for infusion
PRS CK STORM
Drug2 vials of PRS CK STORM (dose B) for infusion.
Adverse Events (AEs)
Number and proportion of subjects experiencing AEs.
Serious adverse events (SAEs)
Number and proportion of subjects experiencing SAEs
Treatment-emergent adverse events (TEAEs)
Number and proportion of subjects experiencing TEAEs
Safety measures: Clinical evaluation through physical examination
Number and proportion of subjects with abnormal findings of physical examination parameters (head, ears, Nervous system,Gastrointestinal system, Respiratory system, Lymph nodes Musculoskeletal system, Neck, Throat, Cardiovascular system, Skin, Nose) will be evaluated
Severity of hypoxemia
Severity of hypoxemia measured as changes in SpO2/FiO2 ratio. Severity according to SpO2/FiO2 values is classified as: * Normal: SpO2/FiO2 greater than 299 mmHg * Mild: 219 mmHg greater than SpO2/FiO2 and less than or equal to 299 mmHg * Moderate: 139 mmHg greater than SpO2/FiO2 and less than or equal to 219 mmHg * Severe: SpO2/FiO2 less than or equal to 139 mmHg
Death rate
Percentage of participants who died since the beginning of treatment. Death rate at each timepoint will be studied by means of a difference between independent proportions tests
Average hospital stays (in days)
Average of days that participants stay in the hospital
Participants requiring admission to Intensive Care Unit (ICU)
Percentage of participants requiring admission to ICU
Variations in anti-inflamatory cytokine levels
Changes in the concentrations of anti-inflammatory (TIMP-1 and IL-1Ra) cytokines before and after treatment. Blood samples will be collected from participants to carry out cytokine quantification
Variation in pro-inflammatory cytokine levels
Changes in the concentrations of pro-inflammatory (TNF-α, IL-1β, IL-6 and IL-18) cytokines before and after treatment. Blood samples will be collected from participants to carry out cytokine quantification.
Severity of hypoxemia measured as SpO2/FiO2 ratio considering relevant risk factors as covariates
Severity of hypoxemia measured as changes in SpO2/FiO2 ratio. Severity according to SpO2/FiO2 values is classified as: * Normal: SpO2/FiO2 greater than 299 mmHg * Mild: 219 mmHg greater than SpO2/FiO2 and less than or equal to 299 mmHg * Moderate: 139 mmHg greater than SpO2/FiO2 and less than or equal to 219 mmHg * Severe: SpO2/FiO2 less than or equal to 139 mmHg The association between severity of hypoxemia and the treatment regimen will be assessed, adjusting for the following covariates (as they are considered as risk factors): age, obesity, smoking status, sex, high levels of pro-inflammatory cytokines at baseline, hypertension, SIRS cause (SARS-Cov-2, influenza A, influenza B and RSV); previous SARS-Cov-2, influenza A, influenza B and RSV vaccination; number of previous SARS-Cov-2, influenza A, influenza B and RSV infections; Charlson index at screening period; Chronic Obstructive Pulmonary Disease (COPD); diabetes and heart failure
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