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| Name (Synonyms) | Correlation | |
|---|---|---|
| drug4680 | Virtual home visits Wiki | 0.17 |
| drug2158 | Interferon-β1a Wiki | 0.17 |
| drug2587 | Mesenchymal stem cell therapy Wiki | 0.17 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug4418 | Ticagrelor Wiki | 0.17 |
| drug1467 | Electrical Impedance tomography Wiki | 0.17 |
| drug1996 | Hydroxychloroquine, Clindamycin, Primaquine - high dose. Wiki | 0.17 |
| drug4386 | Therapeutic Plasma exchange Wiki | 0.17 |
| drug3351 | Prasugrel Wiki | 0.17 |
| drug1535 | Eritoran Wiki | 0.17 |
| drug2154 | Interferon-Alpha2B Wiki | 0.17 |
| drug2405 | Low dose Interferon-beta 1a Wiki | 0.17 |
| drug1873 | Heparin - Therapeutic dosage Wiki | 0.17 |
| drug1872 | Heparin - Prophylactic dosage Wiki | 0.17 |
| drug2629 | Mindfulness Rounds Wiki | 0.17 |
| drug2085 | Immunoglobulin Wiki | 0.17 |
| drug1146 | Convalescent Serum Wiki | 0.17 |
| drug3305 | Pleth variability index Wiki | 0.17 |
| drug1676 | Five-days oseltamivir Wiki | 0.17 |
| drug294 | Amoxicillin-clavulanate Wiki | 0.17 |
| drug2087 | Immunoglubulins Wiki | 0.17 |
| drug239 | Adsorbed COVID-19 (inactivated) Vaccine Wiki | 0.17 |
| drug1680 | Fixed-duration higher dose Hydrocortisone Wiki | 0.17 |
| drug1651 | Favipiravir Combined With Tocilizumab Wiki | 0.17 |
| drug1113 | Continuous renal replacement therapy Wiki | 0.17 |
| drug3192 | Piperacillin/tazobactam Wiki | 0.17 |
| drug2684 | Moxifloxacin or Levofloxacin Wiki | 0.17 |
| drug3424 | Protocolised mechanical ventilation strategy Wiki | 0.17 |
| drug931 | Ceftriaxone Wiki | 0.17 |
| drug1175 | Corticosteroid injection Wiki | 0.17 |
| drug1994 | Hydroxychloroquine, Azithromycin Wiki | 0.17 |
| drug5291 | ventilatory support with oxygen therapy Wiki | 0.17 |
| drug1998 | Hydroxychloroquine, Doxycycline Wiki | 0.17 |
| drug1995 | Hydroxychloroquine, Clindamycin Wiki | 0.17 |
| drug3937 | Serological testing Wiki | 0.17 |
| drug4559 | Ultra-Low-dose radiotherapy Wiki | 0.17 |
| drug1679 | Fixed-duration Hydrocortisone Wiki | 0.17 |
| drug579 | Bempegaldesleukin Wiki | 0.17 |
| drug4344 | Ten-days oseltamivir Wiki | 0.17 |
| drug3191 | Piperacillin-tazobactam Wiki | 0.17 |
| drug1892 | High dose Interferon-beta 1a Wiki | 0.17 |
| drug1997 | Hydroxychloroquine, Clindamycin, Primaquine - low dose. Wiki | 0.17 |
| drug2495 | MVC-COV1901 Wiki | 0.17 |
| drug930 | Ceftaroline Wiki | 0.17 |
| drug1958 | Hydroxychloroquine + lopinavir/ritonavir Wiki | 0.17 |
| drug4898 | conjunctival RT PCR Wiki | 0.17 |
| drug2734 | NO-Immunosuppressive Wiki | 0.17 |
| drug3965 | Shock-dependent hydrocortisone Wiki | 0.17 |
| drug2089 | Immunosuppressive Wiki | 0.17 |
| drug4233 | Synthetic neutralising antibodies Wiki | 0.17 |
| drug3125 | Pembrolizumab (MK-3475) Wiki | 0.17 |
| drug2501 | Macrolide administered for 3-5 days Wiki | 0.17 |
| drug2502 | Macrolide administered for up to 14 days Wiki | 0.17 |
| drug297 | Anakinra Wiki | 0.15 |
| drug382 | Aspirin Wiki | 0.15 |
| drug2376 | Lopinavir-Ritonavir Wiki | 0.12 |
| drug2414 | Low molecular weight heparin Wiki | 0.12 |
| drug3895 | Self Supportive Care (SSC) Alone Wiki | 0.12 |
| drug3052 | PLX-PAD Wiki | 0.12 |
| drug4387 | Therapeutic anticoagulation Wiki | 0.12 |
| drug2385 | Lopinavir/ritonavir Wiki | 0.12 |
| drug1174 | Corticosteroid Wiki | 0.12 |
| drug2261 | KB109 + Self Supportive Care (SSC) Wiki | 0.12 |
| drug3980 | Simvastatin Wiki | 0.12 |
| drug4151 | Stellate Ganglion Block Wiki | 0.12 |
| drug4280 | TY027 Wiki | 0.10 |
| drug3970 | Siltuximab Wiki | 0.10 |
| drug1015 | Clopidogrel Wiki | 0.10 |
| drug5106 | observational Wiki | 0.10 |
| drug364 | Apremilast Wiki | 0.10 |
| drug1293 | Dexamethasone Wiki | 0.10 |
| drug17 | 0.9% saline Wiki | 0.10 |
| drug3635 | Remdesivir Wiki | 0.09 |
| drug2606 | Methylprednisolone Wiki | 0.09 |
| drug2381 | Lopinavir/Ritonavir Wiki | 0.08 |
| drug453 | Azithromycin Wiki | 0.08 |
| drug588 | Best Practice Wiki | 0.07 |
| drug1150 | Convalescent plasma Wiki | 0.07 |
| drug3876 | Sarilumab Wiki | 0.07 |
| drug1950 | Hydroxychloroquine Wiki | 0.07 |
| drug1766 | Gam-COVID-Vac Wiki | 0.06 |
| drug2387 | Losartan Wiki | 0.06 |
| drug4593 | Usual Care Wiki | 0.05 |
| drug4102 | Standard of Care Wiki | 0.05 |
| drug1043 | Colchicine Wiki | 0.05 |
| drug4690 | Vitamin C Wiki | 0.04 |
| drug3290 | Placebos Wiki | 0.04 |
| drug1644 | Favipiravir Wiki | 0.03 |
| drug3195 | Placebo Wiki | 0.03 |
| drug1135 | Convalescent Plasma Wiki | 0.03 |
| drug4112 | Standard of care Wiki | 0.03 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| D055501 | Macrophage Activation Syndrome NIH | 0.17 |
| D030341 | Nidovirales Infections NIH | 0.12 |
| D011014 | Pneumonia NIH | 0.11 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| D045888 | Ganglion Cysts NIH | 0.10 |
| D018352 | Coronavirus Infections NIH | 0.07 |
| D003333 | Coronaviridae Infections NIH | 0.07 |
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.07 |
| D007676 | Kidney Failure, Chronic NIH | 0.07 |
| D012327 | RNA Virus Infections NIH | 0.06 |
| D003324 | Coronary Artery Disease NIH | 0.06 |
| D011024 | Pneumonia, Viral NIH | 0.06 |
| D014777 | Virus Diseases NIH | 0.05 |
| D009369 | Neoplasms, NIH | 0.05 |
| D013577 | Syndrome NIH | 0.04 |
| D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.04 |
| D055371 | Acute Lung Injury NIH | 0.04 |
| D020521 | Stroke NIH | 0.04 |
| D008173 | Lung Diseases, Obstructive NIH | 0.04 |
| D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.04 |
| D007239 | Infection NIH | 0.04 |
| D012128 | Respiratory Distress Syndrome, Adult NIH | 0.04 |
| D018450 | Disease Progression NIH | 0.04 |
| D012140 | Respiratory Tract Diseases NIH | 0.03 |
| D007249 | Inflammation NIH | 0.03 |
| D002318 | Cardiovascular Diseases NIH | 0.03 |
| D012141 | Respiratory Tract Infections NIH | 0.02 |
| D016638 | Critical Illness NIH | 0.02 |
| D003141 | Communicable Diseases NIH | 0.01 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0002090 | Pneumonia HPO | 0.11 |
| HP:0001677 | Coronary artery atherosclerosis HPO | 0.06 |
| HP:0002664 | Neoplasm HPO | 0.05 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0001297 | Stroke HPO | 0.04 |
| HP:0006536 | Pulmonary obstruction HPO | 0.04 |
| HP:0006510 | Chronic pulmonary obstruction HPO | 0.04 |
| HP:0001626 | Abnormality of the cardiovascular system HPO | 0.03 |
| HP:0011947 | Respiratory tract infection HPO | 0.02 |
Navigate: Correlations HPO
There are 36 clinical trials
REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia. In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19.
Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and not receiving organ support in ICU Time: Day 21Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 monthsDescription: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital
Measure: Destination at time of hospital discharge Time: Free text Day 90Description: Antibiotic Domain specific outcome
Measure: Occurrence of multi-resistant organism colonisation/infection Time: Day 90, censored at hospital dischargeDescription: Antibiotic Domain specific outcome
Measure: Occurrence clostridium difficile Time: Day 90, censored at hospital dischargeDescription: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.
Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death Time: Day 90, censored at hospital dischargeDescription: Antiviral Domain specific outcome. Only required at selected sites.
Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens Time: Day 3, up to Day 7Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint
Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing) Time: Day 90, censored at hospital dischargeSome patients infected with the COVID-19 can develop uncontrolled immune response, leading to potentially life-threatening damage to lung tissue. Tocilizumab was first approved by the U.S. FDA in 2010 for rheumatoid arthritis and might now be used to treat serious COVID-19 patients with lung damage, according to China's National Health Commission updated its treatment guidelines in 7th version.Continuous Renal Replacement Therapy (CRRT) was recommended by China's National Health Commission treatment guidelines in 1st-7th version to control sever COVID-19 patients.
Description: This is a composite outcome measure. Criteria for fever normalization: Temperature < 36.6 °C armpit, < 37.2 °C oral sustained for at least 72 hours and criteria for oxygen normalization: peripheral capillary oxygen saturation (Sp02) > 94% sustained for at least 72 hours.
Measure: Proportion of Participants With Normalization of Fever and Oxygen Saturation Through Day 14 Time: First dose date up to 14 daysDescription: Measured in days
Measure: Duration of hospitalization Time: Up to 28 daysDescription: Criteria for: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for at least 72 hours.
Measure: Proportion of Participants With Normalization of Fever Through Day 14 Time: First dose date up to 14 daysDescription: Blood routine test
Measure: Change from baseline in white blood cell and differential count Time: Day 1 through Day 28Description: Oropharyngeal or anal swabs
Measure: Time to first negative in 2019 novel Corona virus RT-PCR test Time: Up to 28 daysDescription: Date and cause of death (if applicable).
Measure: All-cause mortality Time: up to 12 weeksDescription: Serum hsCRP
Measure: Change from baseline in hsCRP Time: Day 1 through Day 28Description: Serum inflammatory cytokines
Measure: Change from baseline in cytokines IL-1β, IL-10, sIL-2R, IL-6, IL-8 and TNF-α Time: Day 1 through Day 28Description: Flow cytometry for peripheral whole blood
Measure: Change from baseline in proportion of CD4+CD3/CD8+CD3 T cells Time: Day 1 through Day 28 (if applicable)The purpose of this study is to evaluate the efficacy and safety of favipiravir combined with tocilizumab in the treatment of corona virus disease 2019.
Description: Definition of clinical cure: The viral load of the respiratory specimen was negative for two consecutive times (the interval between the two tests was greater than or equal to one day), the lung image improved, and the body temperature returned to normal for more than 3 days, and the clinical manifestation improved.
Measure: Clinical cure rate Time: 3 monthsIn a Phase 2 Simon's Optimal Two-Stages Design intravenous tocilizumab will be administered as single 8mg/Kg dose in patients affected by severe multifocal interstitial pneumonia correlated to SARS-CoV2 infection. Aim of the study is to test the hypothesis that an anti-IL6 treatment can be effective in calming the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing naso-tracheal intubation and/or death.
Description: rate of patients with no need in increase of FiO2 to maintain stable SO2 and no need of intubation
Measure: arrest in deterioration of pulmonary function Time: 7daysDescription: rate of patients with change of oxygen saturation >3 percentage points or >10% or decrease in FiO2 need or reduction in pulmonary consolidations >30% at HR CT-scan
Measure: improving in pulmonary function Time: 7 daysDescription: rate of patients needed of intubation
Measure: need of oro-tracheal intubation Time: +7 daysDescription: rate of patients dead
Measure: death Time: 14daysThe purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6 and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome
Description: defined as the time from randomization to either an improvement of two points on a six-category ordinal scale or discharge from the hospital: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Time to Clinical Improvement Time: at day 15Description: defined as independece from supplemental oxygen
Measure: Time to improvement in oxygenation Time: during hospital admission (up to 28 days)Description: defined by Pa02/FiO2 ratio while breading room air
Measure: Mean change in oxygenation Time: day 1, day 15 or hospital discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score (Sequential Organ Failure Assessment) between day 1 and day 7 Time: Day 1, day 7or hospital discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 15 Time: day 1, day 15 or hospital discharge, whichever is firstDescription: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale in relation to serum IL-1 Time: at day 15 or hospital discharge, whichever is firstDescription: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale in relation to serum IL-6 Time: at day 15 or hospital discharge, whichever is firstDescription: defined by Hs (Hemophagocytic Syndrome) score
Measure: incidence of secondary haemophagocytic lymphohistiocytosis Time: during hospital admission (up to 28 days)Description: defined by Hs score
Measure: Incidence of secondary haemophagocytic lymphohistiocytosisscore in relation to serum IL-1 Time: during hospital admission (up to 28 days)Description: defined by Hs score
Measure: Incidence of secondary haemophagocytic lymphohistiocytosis in relation to serum IL-6 Time: during hospital admission (up to 28 days)Coronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. Hypotheses: 1. Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death. 2. Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death. Objectives: 1. To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize. 2. To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
Description: Tmax Response: Resolution of fever (from Tmax > 38C in 24H period to Tmax < 38C in following 24H period, with Tmax measured by commonly accepted clinical methods [forehead, tympanic, oral, axillary, rectal]). Maximum temperature within 24-hour period of time (0:00-23:59) on the day prior to, day of, and every 24 hours after tocilizumab administration. The primary endpoint is absence of Tmax greater than or equal to 38ºC in the 24-hour period following tocilizumab administration.
Measure: Clinical response Time: Assessed for the 24 hour period after tocilizumab administrationDescription: CRP normalization rate: Calculated as the ratio of the number of patients who achieve normal CRP value following tocilizumab administration and total number of patients who receive tocilizumab. Time to CRP normalization: Calculated as the number of hours between tocilizumab administration and first normal CRP value.
Measure: Biochemical response Time: Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administrationDescription: 28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.
Measure: Overall survival Time: 28 daysDescription: This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.
Measure: Survival to hospital discharge Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).
Measure: Progression of COVID-19 pneumonitis Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.
Measure: Rate of non-elective mechanical ventilation Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).
Measure: Duration of mechanical ventilation Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Measure: Time to mechanical ventilation Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.
Measure: Rate of vasopressor/inotrope utilization Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).
Measure: Duration of vasopressor/inotrope utilization Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.
Measure: Time to vasopressor or inotropic utilization Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationDescription: Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.
Measure: Number of ICU days Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.
Measure: Duration of Increased Supplemental Oxygen Requirement from Baseline Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationCoronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. Hypotheses: 1. Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death. 2. Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death. Objectives: 1. To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize. 2. To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
Description: Tmax Response: Resolution of fever (from Tmax > 38C in 24H period to Tmax < 38C in following 24H period, with Tmax measured by commonly accepted clinical methods [forehead, tympanic, oral, axillary, rectal]). Maximum temperature within 24-hour period of time (0:00-23:59) on the day prior to, day of, and every 24 hours after tocilizumab administration. The primary endpoint is absence of Tmax greater than or equal to 38ºC in the 24-hour period following tocilizumab administration.
Measure: Clinical response Time: Assessed for the 24 hour period after tocilizumab administrationDescription: CRP normalization rate: Calculated as the ratio of the number of patients who achieve normal CRP value following tocilizumab administration and total number of patients who receive tocilizumab. Time to CRP normalization: Calculated as the number of hours between tocilizumab administration and first normal CRP value.
Measure: Biochemical response Time: Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administrationDescription: 28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.
Measure: Overall survival Time: 28 daysDescription: This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.
Measure: Survival to hospital discharge Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).
Measure: Progression of COVID-19 pneumonitis Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.
Measure: Rate of non-elective mechanical ventilation Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).
Measure: Duration of mechanical ventilation Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Measure: Time to mechanical ventilation Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.
Measure: Rate of vasopressor/inotrope utilization Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).
Measure: Duration of vasopressor/inotrope utilization Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.
Measure: Time to vasopressor or inotropic utilization Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationDescription: Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.
Measure: Number of ICU days Time: Hospitalization, up to 4 weeks after tocilizumab administrationDescription: Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.
Measure: Duration of Increased Supplemental Oxygen Requirement from Baseline Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administrationThe overall objective of the study is to determine the therapeutic effect and tolerance of Tocizilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the COVIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
Description: Group 1. Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14. Group 1 Time: 14 daysDescription: Group 1. Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale <=5 at day 4. Group 1. Time: 4 daysDescription: Group 2. Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14. Group 2. Time: 14 daysDescription: Group 2 Early end point : proportion of patients with a decrease of WHO score of at least 1 point at day 4. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale at day 4. Group 2. Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: respiratory acidosis at day 4 Time: 4 daysDescription: evolution of PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: time to oxygen supply independency
Measure: time to oxygen supply independency Time: 14 daysDescription: duration of hospitalization
Measure: duration of hospitalization Time: 90 daysDescription: time to negative viral excretion
Measure: time to negative viral excretion Time: 90 daysDescription: time to ICU discharge
Measure: time to ICU discharge Time: 90 daysDescription: time to hospital discharge
Measure: time to hospital discharge Time: 90 daysCOVID-19 is a respiratory disease caused by the new coronavirus (SARS-CoV-2) and causes considerable morbidity and mortality. Currently, there is no vaccine or therapeutic agent to prevent and treat a SARS-CoV-2 infection. This clinical trial is designed to evaluate the use of Tocilizumab in combination with hydroxychloroquine and azithromycin for the treatment of hospitalized adult patients with COVID-19.
This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial
Description: Assessed by hospital records
Measure: Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes Time: through day 14 after study treatment initiationDescription: Assessed by hospital records
Measure: Proportion of patients discharged from the emergency department and classified as low risk Time: through End of Study, defined as 90 ± 14 days after study entryDescription: Assessed by hospital records
Measure: Number of days of patient hospitalization Time: through End of Study, defined as 90 ± 14 days after study entryDescription: The clinical status will be assessed by the SOFA scores
Measure: Change from baseline in organ failure parameters Time: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first.Description: Determined as percentage of dead patients
Measure: Proportion of mortality rate Time: through End of Study, defined as 90 ± 14 days after study entryDescription: Determined as: Time to invasive mechanical ventilation (if not previously initiated); Time to independence from non-invasive mechanical ventilation; Time to independence from oxygen therapy.
Measure: Analysis of the remission of respiratory symptoms Time: through End of Study, defined as 90 ± 14 days after study entryDescription: by using the same imaging technique (chest X-ray or thoracic CT scan)
Measure: Evaluation of the radiological response Time: at days 1 and 28 (+/- 2 days)Description: determined using oropharyngeal or anal swabs
Measure: Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test Time: within 28 days from study inclusionDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of hemoglobin Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of platelets Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of activated partial thromboplastin time (aPTT) Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of creatinine Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of glucose Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of total bilirubin Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Baseline defined as the value collected at day 1, 2 hours before treatment administration
Measure: Change from baseline of albumin Time: days 3, 5, 7, 10, 14 and 28 after administration of study drugDescription: Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.
Measure: Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability) Time: Up to End of Study, defined as 90 ± 14 days after study entryOur aim is to conduct one trial of personalized immunotherapy in patients with SARS-CoV-2 (COVID-19) associated with organ dysfunction and with laboratory findings of macrophage activation syndrome or immune dysregulation. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be allocated to immunotherapy treatment according to their needs.
Description: At least 25% decrease between baseline sequential organ failure assessment SOFA score and measured sequential organ failure assessment SOFA score at Study Day 8
Measure: Change of baseline total sequential organ failure assessment (SOFA) score Time: Visit study day 8Description: Resolution of all criteria of lower respiratory tract involvemed that led to study inclusion (except findings from imaging studies) at Study Day 8
Measure: Improvement of lung involvement measurements Time: Visit study day 8Description: At least 50% increase of pO2/FiO2 ratio between baseline and study visit Day 8
Measure: Increase of pO2/FiO2 ratio Time: Visit Study Day 8Description: Change of total sequential organ failure assessment (SOFA) score between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Comparison of change of baseline total sequential organ failure assessment (SOFA) score in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Change of lung involvement measurements between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of change of lung involvement measurements in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Comparison of increase in pO2/FiO2 ratio towards historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of pO2/FiO2 ratio in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Change of Sequential organ failure assessment (SOFA) score on day 28 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of sequential organ failure assessment (SOFA) score Time: Day 28Description: Mortality on day 28
Measure: Rate of Mortality Time: Day 28Description: Mortality on day 90
Measure: Rate of Mortality Time: Day 90Description: Cytokine stimulation from peripheral blood mononuclear cells will be compared between days 0 and 4
Measure: Cytokine stimulation Time: Screening, Day 4Description: Gene expression of peripheral blood mononuclear cells will be compared between days 0 and 4
Measure: Gene expression Time: Screening, Day 4Description: Change of serum/plasma proteins between days 0 and 4
Measure: Serum/plasma proteins Time: Screening, Day 4Description: Classification of immune function of screened patients who are not enrolled in study drug since they are not characterized with MAS or immune dysregulation
Measure: Classification of the immune function Time: ScreeningThis study aims to compare the efficacy and safety of Methylprednisolone versus Tocilizumab in improving clinical outcomes and reducing the need for ventilator support in COVID-19 patients with moderate COVID-19 disease at risk for complications of cytokine storm. Approximately 310 participants hospitalized with COVID-19 in UMMC, Hospital Sungai Buloh, Hospital Kuala Lumpur and Hospital Tuanku Jaafar will be enrolled into this study. Eligible participants will be selected based on a set of clinical, laboratory and radiological parameters indicative of early stages of CRS and lung function decline prior to being randomized at a ratio of 1:1 to receive either Tocilizumab or Methylprednisolone. Participants will be monitored daily for clinical and laboratory parameters, and at 48 hours, switched to the alternate study arm should they manifest signs and symptoms indicative of decompensation.
The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.
Description: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours
Measure: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation Time: two weeks from participants' allocation to study armDescription: Death
Measure: Death from any cause Time: Two weeks from participants' allocation to study armDescription: Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale
Measure: Tocilizumab toxicity Time: Two weeks from participants' allocation to study armDescription: Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment
Measure: Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment Time: Two weeks from participants' allocation to study armDescription: Changes from baseline of the PaO2 / FiO2 ratio
Measure: Evaluate the progress of the PaO2 / FiO2 ratio Time: Two weeks from participants' allocation to study armDescription: Changes from baseline of the lymphocyte count
Measure: Evaluate the trend over time of the lymphocyte count Time: Two weeks from participants' allocation to study armDiagnostic determination of disease and treatment responses has been limited to qualitative imaging, measurement of serum markers of disease, and sampling of tissue. In each of these instances, there is a built in error either due to sensitivity and specificity issues, clinician interpretation of results, or acceptance of the use of an indirect marker (blood test) of what is happening elsewhere in the body - at the tissue level. The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons [1] provides the first and only patented test (#9566037) - along with the associated submitted patent applications ruled to be covered under #9566037 - that quantitatively measures changes in tissue resulting from inter alia a disease process. This includes inter alia coronary artery disease (CAD), cancer and infectious/inflammatory processes including CoVid-19 pneumonia (CVP) resulting from the metabolic and regional blood flow differences (RBFDs) caused by these diseases. The purpose of this paper is to make clinicians and researchers aware of this proposed method for investigating the prevalence and severity of CVP - in addition to providing rapid determination of treatment response in each patient, directing treatment decisions; thereby reducing the loss of time, money, resources and patient lives.
Description: Measured improvement in tissue as measured using FMTVDM
Measure: Improvement in FMTVDM Measurement with nuclear imaging. Time: 72 hoursDescription: Extubation
Measure: Ventilator status Time: 7 daysDescription: Self explanatory
Measure: Survival status Time: 30 daysThis is a randomized, double blind, multi-center study to evaluate the effects of tocilizumab compared to placebo on patient outcomes in participants with confirmed SARS-CoV-2 infection and evidence of systemic inflammation. The aim of this study is to test the effect of Tocilizumab on multi-organ dysfunction in a phase 3 randomized controlled trial among hospitalized patients with COVID-19 infection. Specifically, as compared to placebo, we will test whether tocilizumab is associated with a reduction in multi-organ dysfunction among hospitalized COVID-19 adult patients with elevated inflammatory measures. Multi-organ dysfunction will be measured as the incidence of the following composite endpoint (mechanical ventilation, renal replacement therapy, mechanical support, need for inotropes or vasopressors, liver dysfunction (increased bilirubin), and all-cause mortality). We will also assess multiple pre-specified secondary (exploratory) endpoints and safety endpoints. We hypothesize that, as compared to placebo, tocilizumab will reduce transfer to the ICU, need for mechanical ventilation, increase rates of hospital discharge in patients diagnosed with severe COVID-19 infection and evidence of exaggerated inflammatory response.
Description: The primary endpoint is the time from administration of the investigational agent (or placebo) to requiring mechanical ventilation and intubation, or death for subjects who die prior to intubation
Measure: The primary endpoint is the time from administration of the investigational agent (or placebo) to requiring mechanical ventilation and intubation, or death for subjects who die prior to intubation Time: 28 daysDescription: Time to improvement will be assessed by changes in subjects' status, ranked on the ordinal scale: Clinical Improvement Scale Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or <= 2L supplemental oxygen) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g. vasopressors, renal replacement therapy) Death Higher scores indicate a worse outcome.
Measure: Time from investigational medication (or placebo) to at least one point worsening on clinical improvement scale for subjects requiring supplemental oxygen (score >= 3) at baseline, or at least two point worsening otherwise (score = 2 at baseline Time: 28 daysDescription: Time from administration of the investigational agent (or placebo) to absence of the need for supplemental oxygen among those who require at least supplemental oxygen at baseline
Measure: Time from administration of the investigational agent (or placebo) to absence of the need for supplemental oxygen among those who require at least supplemental oxygen at baseline Time: 28 daysDescription: Time to improvement will be assessed by changes in subjects' status, ranked on the ordinal scale: Clinical Improvement Scale Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or <= 2L supplemental oxygen) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g. vasopressors, renal replacement therapy) Death Higher scores indicate a worse outcome.
Measure: Time to first improvement from baseline of at least 2 points (or the maximum amount) on the ordinal scale given in Table 2. Time: 28 daysDescription: Time to absence of the need for supplemental oxygen will be measured from time of investigational treatment administration. We will use the same approach as that employed for the comparison of time to clinical improvement. Only subjects on supplemental oxygen at the time of randomization will contribute to this analysis. Subjects who die will be censored at 29 days, and the groups will be compared using a stratified log-rank test and stratified Cox proportional hazards model. The duration of supplemental oxygen will be compared between the groups. For this analysis, we will include all subjects in the analysis by assigning all subjects who did not receive supplemental oxygen a value of 0. Subjects who died following supplemental oxygen will be given a value of the number of days from when supplemental oxygen began until the end of the follow-up period. The groups will be compared using a Wilcoxon rank sum test.
Measure: Time from initiation of supplemental oxygen to end of supplemental oxygen use during 28-day study follow-up period. Time: 28 daysDescription: Time to death will be measured from the time the investigational medication is administered until the time of the subject's death. We will compare the groups using a stratified log-rank test and estimate the hazard ratio comparing the groups using a stratified Cox proportional hazards model.
Measure: Time from administration of the investigational agent (or placebo) to death Time: 28 daysDescription: Time to intubation will be measured from time of investigational treatment administration to the time of intubation. For this analysis, death will be treated as a competing risk. The analysis will compare the cause-specific hazard in the treatment groups using a Cox proportional hazards model. We will also compare the cumulative incidence functions between groups using the approach of Fine and Gray.
Measure: Time from administration of the investigational medication (or placebo) to intubation. Time: 28 daysDescription: Mortality at 28 days will be compared using a Mantel-Haenszel test to allow stratification on study site. The relative risk will be estimated using the Mantel-Haenszel method. If we have missing mortality data on any subjects, we will estimate the proportion of subjects who died in each treatment group using the estimate from the Kaplan-Meier curve in each group. Then, we will compare the two groups using the approaches described in Klein et al (citation: Klein JP, Logan B, Harhoff M, Anderson PK. Analyzing survival curves at a fixed point in time. Statistics in Medicine. 2007;26:4505-4519.)
Measure: Mortality at 28 days after administration of investigational agent (or placebo). Time: 28 daysDescription: The duration of mechanical ventilation will be compared between the groups using two approaches. First, we will include all subjects in the analysis by assigning all subjects who were not intubated a value of 0. Subjects who died following intubation will be given a value of the number of days from when mechanical ventilation began until the end of the follow-up period. The groups will be compared using a Wilcoxon rank sum test. Second, we will analyze only subjects who were intubated and compare the time on mechanical ventilation using a stratified log-rank test. Subjects who die without being taken off the ventilator will be censored at a duration of mechanical ventilation longer than the longest time.
Measure: Duration of mechanical ventilation during 28-day study follow-up period. Time: 28 daysDescription: The proportion of subjects requiring ICU admission between baseline and 28 days will be measured as the number of subjects requiring ICU admission over their hospitalization over the number of evaluable subjects (i.e., the number of subjects not in the ICU at the time of investigational treatment administration). The groups will be compared using a Mantel-Haenszel test to allow stratification on study site. The relative risk will be estimated using the Mantel-Haenszel method.
Measure: ICU admission or death among those not in the ICU at the time of administration of investigational agent (or placebo). Time: 28 daysDescription: The time to discharge from the hospital in subjects, measured from the time of investigational treatment administration to time of discharge, will be compared using a stratified log-rank test. Subjects who die will be censored at Day 29 to indicate that they never left the hospital during the study.
Measure: Time from administration of the investigational medication (or placebo) to hospital discharge Time: 28 daysDescription: The proportion of adverse events graded by CTCAE v5.0
Measure: Safety and tolerability Time: 28 daysDescription: The raw ordinal scale scores at days 4, 7, 14, 21, and 28 in subjects treated with tocilizumab therapy versus controls will be compared at each time point using a random intercept proportional odds logistic regression model. This model will be used to model all measurements together to estimate the differences between the treatment groups at each time point.
Measure: Ordinal Clinical Improvement Scale (Table 2) score at day: 4, 7, 14, 21, and 28. Time: Days 4, 7, 14, 21, and 28This phase III trial compares the effect of adding tocilizumab to standard of care versus standard of care alone in treating cytokine release syndrome (CRS) in patients with SARS-CoV-2 infection. CRS is a potentially serious disorder caused by the release of an excessive amount of substance that is made by cells of the immune system (cytokines) as a response to viral infection. Tocilizumab is used to decrease the body's immune response. Adding tocilizumab to standard of care may work better in treating CRS in patients with SARS-CoV-2 infection compared to standard of care alone.
Description: The 7-day length of invasive MV for each arm will be estimated with 95% confidence intervals (CIs) using the exact binomial distribution. Their difference by the arms will be tested by Cochran-Mantel-Haenszel (CMH) test stratified by the age group and Sequential Organ Failure Assessment (SOFA) score at significance level of 0.05.
Measure: 7-day length of invasive mechanical ventilation (MV) Time: Up to 7 daysDescription: Defined as death within 30-day after randomization. The 30-day mortality rate for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: 30-day mortality rate Time: Up to 30-day after randomizationDescription: The rate of ICU transfer for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: Rate of intensive care (ICU) transfer Time: Up to 2 yearsDescription: The rate of invasive mechanical ventilation for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: Rate of invasive mechanical ventilation Time: Up to 2 yearsDescription: The rate of tracheostomy for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: Rate of tracheostomy Time: Up to 2 yearsDescription: Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test
Measure: Length of ICU stay Time: Up to 2 yearsA phase II clinical trial will be carried out with the objective of studying the impact of the administration of Tocilizumab on the evolution of the acute respiratory distress syndrome (ARDS) in patients with severe or critical SARS-CoV-2 infection. Due to the high mortality of severe forms of SARS-CoV-2 and for ethical reasons, a control arm will not be included. Patients will be recruited by signing an informed consent and the baseline variables of interest will be recorded. Tocilizumab will be administered in one or two doses, depending on the case, and will be followed up for 30 days. The response to treatment, survival and evolution will be studied. Factors associated with improvement of ARDS and survival will be identified through multivariate analyzes. The results will be compared with those reported internationally.
Description: Until removal of mechanical ventilation, Control of hemoglobin, hematocrit, platelet , and leukocytes levels.
Measure: Hematic biometry Time: 24 hoursDescription: Until removal of mechanical ventilation. Control of glucose, uric acid, cholesterol, urea, triglycerides, and creatinine.
Measure: Blood chemistry Time: 24 hoursDescription: Until removal of mechanical ventilation. Control metabolic and repiratory alcalosis or acidosis.
Measure: Blood gas Time: 24 hoursDescription: Until removal of mechanical ventilation, Control of hemoglobin, hematocrit, platelet , and leukocytes levels.
Measure: Hematic biometry Time: 48 hoursDescription: Until removal of mechanical ventilation. Control of glucose, uric acid, cholesterol, urea, triglycerides, and creatinine.
Measure: Blood chemistry Time: 48 hoursDescription: Until removal of mechanical ventilation. Control metabolic and repiratory alcalosis or acidosis.
Measure: blood gas Time: 48 hoursDescription: Until removal of mechanical ventilation, Control of hemoglobin, hematocrit, platelet , and leukocytes levels.
Measure: Hematic biometry Time: 72 hoursDescription: Until removal of mechanical ventilation. Control of glucose, uric acid, cholesterol, urea, triglycerides, and creatinine.
Measure: Blood chemistry Time: 72 hoursDescription: Until removal of mechanical ventilation. Control metabolic and repiratory alcalosis or acidosis.
Measure: blood gas Time: 72 hoursDescription: Until removal of mechanical ventilation, Control of hemoglobin, hematocrit, platelet , and leukocytes levels.
Measure: Hematic biometry Time: 7 daysDescription: Until removal of mechanical ventilation. Control of glucose, uric acid, cholesterol, urea, triglycerides, and creatinine.
Measure: Blood chemistry Time: 7 daysDescription: Until removal of mechanical ventilation. Control metabolic and repiratory alcalosis or acidosis.
Measure: blood gas Time: 7 daysDescription: Until removal of mechanical ventilation, Control of hemoglobin, hematocrit, platelet , and leukocytes levels.
Measure: Hematic biometry Time: 14 daysDescription: Until removal of mechanical ventilation. Control of glucose, uric acid, cholesterol, urea, triglycerides, and creatinine.
Measure: Blood chemistry Time: 14 daysDescription: Until removal of mechanical ventilation. Control metabolic and repiratory alcalosis or acidosis.
Measure: blood gas Time: 14 daysDescription: Until removal of mechanical ventilation. Monitoring for signs of pneumonia imaging.
Measure: thorax radiography Time: 24 hoursDescription: Until removal of mechanical ventilation. Monitoring for signs of pneumonia imaging.
Measure: thorax radiography Time: 7 daysDescription: Until removal of mechanical ventilation. Monitoring for signs of pneumonia imaging.
Measure: thorax radiography Time: 14 daysThis phase II expanded access trial will study how well tocilizumab works in reducing the serious symptoms including pneumonitis (severe acute respiratory distress) in patients with cancer and COVID-19. COVID-19 is caused by the SARS-CoV-2 virus. COVID-19 can be associated with an inflammatory response by the immune system which may also cause symptoms of COVID-19 to worsen. This inflammation may be called "cytokine storm," which can cause widespread problems in the body. Tocilizumab is a medicine designed to block the action of a protein called interleukin-6 (IL-6) that is involved with the immune system and is known to be a key factor for problems with excessive inflammation. Tocilizumab is effective in treating "cytokine storm" from a type of cancer immunotherapy and may be effective in reducing the inflammatory response and "cytokine storm" seen in severe COVID-19 disease. Treating the inflammation may help to reduce symptoms, improve the ability to breathe without a breathing machine (ventilator), and prevent patients from having more complications.
This study (EMPACTA) will a) evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia, and b) include an optional substudy to explore the long-term sequelae of resolved COVID-19 pneumonia.
The purpose of this study is to find out whether the study drug tocilizumab is an effective treatment for COVID-19 infection.
Description: The primary endpoint for this cohort is progression of respiratory failure (binary yes/no while hospitalized). Progression of respiratory failure will be defined as a sustained increase in oxygen requirement (FiO2) or need for intubation/mechanical ventilation.
Measure: Progression of respiratory failure or death Time: 14 daysTitle: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation. This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death. This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.
Description: One-month mortality rate .
Measure: Survival Time: One-monthRECOVERY is a randomised trial investigating whether treatment with Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin, Colchicine, IV Immunoglobulin (children only), Convalescent plasma, Synthetic neutralizing antibodies (REGN-COV2), Tocilizumab or Aspirin prevents death in patients with COVID-19.
Description: For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.
Measure: All-cause mortality Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of days stay in hospital
Measure: Duration of hospital stay Time: Within 28 days and up to 6 months after the main randomisationDescription: Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO.
Measure: Composite endpoint of death or need for mechanical ventilation or ECMO Time: Within 28 days and up to 6 months after the main randomisationDescription: To assess the effects of study treatment on number of patients who needed ventilation and the number of days it was required
Measure: Need for (and duration of) ventilation Time: Within 28 days and up to 6 months after the main randomisationDescription: To assess the effects of study treatment on number of patients who needed renal replacement therapy
Measure: Need for renal replacement Time: Within 28 days and up to 6 months after the main randomisationDescription: To assess the effects of study treatment on number of patients who develop new major cardiac arrythmias
Measure: Development of new major cardiac arrythmias Time: Within 28 days and up to 6 months after the main randomisationThe host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.
Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 2 Time: At 2 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2 Time: At 2 days after RTDescription: Pa02 / Fi02 > 300 mmHg
Measure: Blood Gas Analysis at Day 2 Time: At 2 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 2 Time: At 2 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 5 Time: At 5 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5 Time: At 5 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 5 Time: At 5 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)
Measure: Oxygen Therapy Status at Day 7 Time: At 7 after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)
Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7 Time: At 7 days after RTDescription: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)
Measure: Blood Test at Day 7 Time: At 7 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)
Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7 Time: At 7 days after RTDescription: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)
Measure: Recovery time Time: From RT administration until hospital discharge or deathDescription: COVID-19 negativization test
Measure: COVID-19 status Time: At 7 days after RTDescription: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)
Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1 Time: At 1 month after RTDescription: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.
Measure: Acute Toxicity Time: 1-3 months after RTThe trial evaluates the efficacy and safety of Tocilizumab, which rapidly reduces the inflammation process through inhibition of IL-6 in patients with moderate to severe COVID-19 with increased inflammatory markers. There will be two arms in the trial, one receiving the best supportive care, and the other receiving it plus tocilizumab. Patients will be followed until Day 29 after randomization.
Description: Evaluation of clinical status of patients on day 15 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)
Measure: Evaluation of clinical status Time: Day 15 of the trialDescription: All-cause mortality from randomization to day 28
Measure: All-cause mortality Time: 29 days after the randomizationDescription: Deaths that occur during hospital admission.
Measure: Hospital Mortality Time: 29 days after the randomizationDescription: Improvement of SOFA scale of patients at day 8, 15 and 29 after randomization
Measure: Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale Time: 29 days after the randomization (evaluations at D8 and D15)Description: Evaluation of clinical status of patients on the day 8, 22 and 29 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)
Measure: Evaluation of clinical status Time: 29 days after the randomization (evaluations at D8 and D29)Description: Days alive and free from mechanical ventilation since randomization
Measure: Ventilator free days Time: 29 days after the randomizationDescription: Days from randomization to independence of oxygen support
Measure: Time until oxygen support independence Time: 29 days after the randomizationDescription: Number of patients that were not at mechanical ventilation at randomization and that required that support.
Measure: Need of mechanical ventilation support Time: 29 days after the randomizationDescription: Number of days to mechanical ventilation for patients that were not receiving it at randomization. For patients that were not in mechanical ventilation at randomization: number of days until that support was required.
Measure: Days to mechanical ventilation support. Time: 29 days after the randomizationDescription: Lenght of hospitalization stay in survivors (in days)
Measure: Duration of hospitalization Time: 29 days after the randomizationDescription: Incidence of other infections (aside from SARS-CoV 2)
Measure: Other infections Time: 29 days after the randomizationDescription: Incidence of thromboembolic events in patients with COVID-19
Measure: Incidence of thromboembolic events Time: 29 days after the randomizationDescription: Evaluation of adverse events, as well as serious and unexpected adverse events
Measure: Incidence of adverse events Time: 29 days after the randomization (specific evaluations at D8, D15 and D29)Description: Correlation of inflammatory tests and cytokines with clinical outcomes: clinical status (ordinal scale), time to oxygen support independence, ventilator free days, need of mechanical ventilation and mortality
Measure: Correlation of inflammatory tests and cytokines with clinical outcomes Time: 29 days after the randomizationDescription: Evaluation the kinetics of hemostasia exams, inflammatory tests, cytokines, flow cytometry of blood cells, CBC, renal and liver exams
Measure: Exploratory evaluation of laboratory exams during hospitalization Time: 29 days after the randomizationDescription: Evaluation of viral clearance of SARS-CoV2 using RT-PCR analysis of nasopharyngeal swab
Measure: Evaluation of viral clearance of SARS-CoV2 Time: Day 8 and 15 after randomizationThis study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.
Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 60The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g. increase in oxygen requirements). Participants will be followed for 28 days.
Description: Clinical Status 7-point ordinal scale: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death
Measure: Clinical status (on a 7-point ordinal scale) at day 28 Time: up to day 28Description: ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
Measure: Clinical improvement Time: up to day 28Description: iv. Incidence of mechanical ventilation v. Ventilator-free days
Measure: Mechanical Ventilation Time: up to day 28Description: vi. Duration of time on supplemental oxygen
Measure: Oxygenation Time: up to day 28This is a cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%.
Description: Mortality status of participants
Measure: All-cause mortality Time: Assessed at 30 days post treatmentDescription: Uninfected, ambulatory, hospitalized: mild disease, hospitalized: severe disease, death
Measure: Ordinal Scale for evaluating subject clinical status at days 3, 8, 15, 30, 60 post treatment. Time: Assessed at days 3, 8, 15, 30, 60 post treatmentAt present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia. The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.
Description: Calculate the mean time of intubation
Measure: To calulate the time of intubation Time: through study completion, and average of 1 monthDescription: Calculate the mean time with oxygen therapy
Measure: To calculate the time with oxygen therapy Time: through study completion, and average of 1 monthDescription: Calculate the mean time with Non-invasive mechanical ventilation
Measure: To calculate the time with Non-invasive mechanical ventilation Time: through study completion, and average of 1 monthDescription: Number of patients deaths of the total of patients included
Measure: To evaluate mortality rate Time: through study completion, and average of 1 monthDescription: To calculate the mean ofPaO2/FiO2
Measure: To calculate respiratory function parameters Time: through study completion, and average of 1 monthDescription: To calculate the mean of levels of oxygen saturation
Measure: To calculate respiratory function parameters Time: through study completion, and average of 1 monthDescription: To calculate the mean of SaO2/FiO2
Measure: To calculate respiratory function parameters Time: through study completion, and average of 1 monthDescription: Evaluate the lung extension of pneumonia
Measure: To evaluate radiological lung extension Time: through study completion, and average of 1 monthDescription: Evaluate the type of lung affection
Measure: To evaluate radiological evolution Time: through study completion, and average of 1 monthDescription: Days of hospitalization in survivors and/or days at ICU throughout the study
Measure: To describe the duration of hospitalization and ICU use Time: through study completion, and average of 1 monthDescription: Percentage of patients with extracorporeal membrane oxygenation
Measure: To evaluate the requirement of additional organ support Time: through study completion, and average of 1 monthDescription: Percentage of patients with molecular adsorbent recirculating system
Measure: To evaluate the requirement of additional organ support Time: through study completion, and average of 1 monthDescription: Percentage of patients with dialysis
Measure: To evaluate the requirement of additional organ support Time: through study completion, and average of 1 monthDescription: Percentage of patients with other support therapy
Measure: To evaluate the requirement of additional organ support Time: through study completion, and average of 1 monthDescription: Analyze the levels of IL-6
Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers Time: through study completion, and average of 1 monthDescription: Incidence of adverse events
Measure: To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab Time: through study completion, and average of 1 monthDescription: Incidence of adverse events by dose of Tocilizumab
Measure: To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab Time: through study completion, and average of 1 monthDescription: To evaluate the time to RT-PCR virus negativity
Measure: To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity Time: through study completion, and average of 1 monthDescription: Analyze the levels of CRP
Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory Time: through study completion, and average of 1 monthDescription: Analyze the levels of procalcitonin (PCT)
Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory Time: through study completion, and average of 1 monthDescription: Analyze the levels of ID-dimer
Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory Time: through study completion, and average of 1 monthDescription: Analyze the levels of ferritin
Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory Time: through study completion, and average of 1 monthDescription: Indicende of serious adverse events
Measure: To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab Time: through study completion, and average of 1 monthDescription: Indicende of serious adverse events based on dose of Tocilizumab
Measure: To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab Time: through study completion, and average of 1 monthDescription: Indicende of adverse events of special interest based on dose of Tocilizumab
Measure: To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab Time: through study completion, and average of 1 monthDescription: Number of patients deaths of the total of patients included based on dose of Tocilizumab
Measure: To evaluate mortality rate Time: through study completion, and average of 1 monthDescription: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab
Measure: To evaluate respiratory function Time: through study completion, and average of 1 monthDescription: Number of patients deaths of the total of patients included based on severity of disease at the start of the study treatment
Measure: To evaluate mortality rate Time: through study completion, and average of 1 monthDescription: Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment
Measure: To evaluate mortality rate Time: through study completion, and average of 1 monthDescription: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on severity of disease at the start of the study treatment
Measure: To evaluate respiratory function Time: through study completion, and average of 1 monthDescription: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment
Measure: To evaluate respiratory function Time: through study completion, and average of 1 monthThe overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab combined with Dexamethasone in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Dexamethasone alone or Dexamethasone +Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care (including Dexamethasone) treated patients
Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death.
Measure: Survival without needs of ventilator utilization at day 14 Time: day 14Description: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale at day 7 and 14 Time: day 7 and day 14Description: Overall survival
Measure: Overall survival at 14, 28, 60 and 90 days Time: 14, 28, 60 and 90 daysDescription: Cumulative incidence of discharge alive
Measure: Cumulative incidence of discharge alive at 14 and 28 days Time: 14 and 28 daysDescription: Survival without needs of mechanical ventilation at day 1. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of mechanical ventilation at day 1 Time: day 1Description: Cumulative incidence of oxygen supply independency
Measure: Cumulative incidence of oxygen supply independency at 14 and 28 days Time: 14 and 28 daysCOVID-19's high mortality may be driven by hyperinflammation. Interleukin-6 (IL-6) axis therapies may reduce COVID-19 mortality. Retrospective analyses of tocilizumab in severe to critical COVID-19 patients have demonstrated survival advantage and lower likelihood of requiring invasive ventilation following tocilizumab administration. The majority of patients have rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. The investigators hypothesized that a dose of tocilizumab significantly lower than the EMA- and FDA-labeled dose (8mg/kg) as well as the emerging standard of care dose (400mg) may be effective in patients with COVID-19 pneumonitis and hyperinflammation. Advantages to the lower dose of tocilizumab may include lower likelihood of secondary bacterial infections as well as extension of this drug's limited supply. The investigators conducted an adaptive single-arm phase 2 trial (NCT04331795) evaluating clinical and biochemical response to low-dose tocilizumab in patients with COVID-19 pneumonitis and hyperinflammation. This multi-center, prospective, randomized controlled phase 2 trial -- designed as two sub-studies to allow for the possible emergence of data demonstrating the clinical efficacy of tocilizumab 8mg/kg or 400mg -- formally tests the clinical efficacy of low-dose tocilizumab in COVID-19 pneumonia. Sub-Study A Primary Objective A: To establish whether low-dose tocilizumab reduces the time to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation, when compared to a tocilizumab-free standard of care. Hypothesis A: The investigators hypothesize that low-dose tocilizumab, when compared to a tocilizumab-free standard of care, decreases the time to recovery in hospitalized, non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation by three days or more. Sub-Study B Primary Objective B: To establish whether low-dose tocilizumab is near-equivalent to high-dose tocilizumab (400mg or 8 mg/kg) in reducing the time to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation. Hypothesis B: The investigators hypothesize that low-dose tocilizumab is near-equivalent to high-dose tocilizumab in reducing the time to clinical recovery in hospitalized, non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation.
Description: Day of recovery is defined as the first day on which the patient achieves one of the following two categories from the seven-point ordinal scale: 6) Hospitalized, not requiring supplemental oxygen or ongoing medical care or 7) Not hospitalized. Time to recovery is the number of days from randomization to achievement of this status. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.
Measure: Time to Recovery Time: 28 daysDescription: This will be defined as the percentage of patients in a given arm of the study achieving one of the above two categories on the ordinal scale on day 7. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.
Measure: Achievement of Recovery Time: 7 daysDescription: This will be defined as the percentage of patients in a given arm of the study who are alive thirty days following randomization. Patients who are discharged to hospice will be counted as deceased on the day of discharge. Patients who are transitioned to inpatient hospice or inpatient comfort measures only will be counted as deceased on the day of transition.
Measure: Overall Survival Time: 28 daysDescription: This will be defined as the number of days that pass between the day of a patient's randomization and his or her discharge from the hospital.
Measure: Hospital Length of Stay Time: Up to 1 yearDescription: Maximum temperature within 24-hour periods of time immediately prior to, immediately following, and then every 24 hours thereafter randomization. The primary endpoint is a measured Tmax in the 24-hour period immediately following randomization that is lower than the measured Tmax in the 24-hour period immediately preceding randomization.
Measure: Clinical Response: Maximum Temperature (Tmax) Response Time: 24 hoursDescription: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of invasive mechanical ventilation during the course of the patient's COVID-19 infection.
Measure: Clinical Response: Rate of Non-Elective Invasive Mechanical Ventilation Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between initiation and cessation of non-elective invasive mechanical ventilation.
Measure: Clinical Response: Duration of Non-Elective Invasive Mechanical Ventilation Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between randomization and the initiation of non-elective invasive mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Measure: Clinical Response: Time to Non-Elective Invasive Mechanical Ventilation Time: Up to 28 daysDescription: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication.
Measure: Clinical Response: Rate of Vasopressor/Inotrope Utilization Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor medications.
Measure: Clinical Response: Duration of Vasopressor/Inotrope Utilization Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between randomization and the initiation of any vasopressor or inotropic medication. This will be treated as a time-to-event with possible censoring.
Measure: Clinical Response: Time to Vasopressor/Inotrope Utilization Time: Up to 28 daysDescription: This will be an ordinal outcome defined by the number of days counted from randomization over which the participant requires supplemental oxygen in excess over his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.
Measure: Clinical Response: Duration of Increased Supplemental Oxygen from Baseline Time: 28 daysDescription: This will be a binary outcome defined as the presence or absence of a decline in CRP of ≥ 25% from baseline CRP in the 27 +/- 3 hours after tocilizumab administration, as compared to pre-treatment baseline.
Measure: Biochemical Response: C-reactive Protein Response Rate Time: 24 hoursDescription: This will be defined as the percentage of patients in a study arm who develop serious non-COVID-19 viral, bacterial, or fungal infections (e.g., bloodstream infection, hospital-acquired pneumonia, ventilator-associated pneumonia, opportunistic infection) following randomization and up to the 28-day assessment of overall survival.
Measure: Safety: Rate of Secondary Infection Time: 28 daysCOVID-19's high mortality may be driven by hyperinflammation. Interleukin-6 (IL-6) axis therapies may reduce COVID-19 mortality. Retrospective analyses of tocilizumab in severe to critical COVID-19 patients have demonstrated survival advantage and lower likelihood of requiring invasive ventilation following tocilizumab administration. The majority of patients have rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. The investigators hypothesized that a dose of tocilizumab significantly lower than the EMA- and FDA-labeled dose (8mg/kg) as well as the emerging standard of care dose (400mg) may be effective in patients with COVID-19 pneumonitis and hyperinflammation. Advantages to the lower dose of tocilizumab may include lower likelihood of secondary bacterial infections as well as extension of this drug's limited supply. The investigators conducted an adaptive single-arm phase 2 trial (NCT04331795) evaluating clinical and biochemical response to low-dose tocilizumab in patients with COVID-19 pneumonitis and hyperinflammation. This multi-center, prospective, randomized controlled phase 2 trial -- designed as two sub-studies to allow for the possible emergence of data demonstrating the clinical efficacy of tocilizumab 8mg/kg or 400mg -- formally tests the clinical efficacy of low-dose tocilizumab in COVID-19 pneumonia. Sub-Study A Primary Objective A: To establish whether low-dose tocilizumab reduces the time to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation, when compared to a tocilizumab-free standard of care. Hypothesis A: The investigators hypothesize that low-dose tocilizumab, when compared to a tocilizumab-free standard of care, decreases the time to recovery in hospitalized, non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation by three days or more. Sub-Study B Primary Objective B: To establish whether low-dose tocilizumab is near-equivalent to high-dose tocilizumab (400mg or 8 mg/kg) in reducing the time to clinical recovery in patients with COVID-19 pneumonitis and hyperinflammation. Hypothesis B: The investigators hypothesize that low-dose tocilizumab is near-equivalent to high-dose tocilizumab in reducing the time to clinical recovery in hospitalized, non-invasively ventilated patients with COVID-19 pneumonitis and hyperinflammation.
Description: Day of recovery is defined as the first day on which the patient achieves one of the following two categories from the seven-point ordinal scale: 6) Hospitalized, not requiring supplemental oxygen or ongoing medical care or 7) Not hospitalized. Time to recovery is the number of days from randomization to achievement of this status. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.
Measure: Time to Recovery Time: 28 daysDescription: This will be defined as the percentage of patients in a given arm of the study achieving one of the above two categories on the ordinal scale on day 7. Note that the ordinal scale is measured once daily, with the patient's worst clinical status during the 24-hour time period (0:00-23:59) being documented.
Measure: Achievement of Recovery Time: 7 daysDescription: This will be defined as the percentage of patients in a given arm of the study who are alive thirty days following randomization. Patients who are discharged to hospice will be counted as deceased on the day of discharge. Patients who are transitioned to inpatient hospice or inpatient comfort measures only will be counted as deceased on the day of transition.
Measure: Overall Survival Time: 28 daysDescription: This will be defined as the number of days that pass between the day of a patient's randomization and his or her discharge from the hospital.
Measure: Hospital Length of Stay Time: Up to 1 yearDescription: Maximum temperature within 24-hour periods of time immediately prior to, immediately following, and then every 24 hours thereafter randomization. The primary endpoint is a measured Tmax in the 24-hour period immediately following randomization that is lower than the measured Tmax in the 24-hour period immediately preceding randomization.
Measure: Clinical Response: Maximum Temperature (Tmax) Response Time: 24 hoursDescription: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of invasive mechanical ventilation during the course of the patient's COVID-19 infection.
Measure: Clinical Response: Rate of Non-Elective Invasive Mechanical Ventilation Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between initiation and cessation of non-elective invasive mechanical ventilation.
Measure: Clinical Response: Duration of Non-Elective Invasive Mechanical Ventilation Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between randomization and the initiation of non-elective invasive mechanical ventilation. This will be treated as a time-to-event with possible censoring.
Measure: Clinical Response: Time to Non-Elective Invasive Mechanical Ventilation Time: Up to 28 daysDescription: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication.
Measure: Clinical Response: Rate of Vasopressor/Inotrope Utilization Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor medications.
Measure: Clinical Response: Duration of Vasopressor/Inotrope Utilization Time: Up to 28 daysDescription: This will be a continuous outcome defined by the amount of time between randomization and the initiation of any vasopressor or inotropic medication. This will be treated as a time-to-event with possible censoring.
Measure: Clinical Response: Time to Vasopressor/Inotrope Utilization Time: Up to 28 daysDescription: This will be an ordinal outcome defined by the number of days counted from randomization over which the participant requires supplemental oxygen in excess over his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.
Measure: Clinical Response: Duration of Increased Supplemental Oxygen from Baseline Time: 28 daysDescription: This will be a binary outcome defined as the presence or absence of a decline in CRP of ≥ 25% from baseline CRP in the 27 +/- 3 hours after tocilizumab administration, as compared to pre-treatment baseline.
Measure: Biochemical Response: C-reactive Protein Response Rate Time: 24 hoursDescription: This will be defined as the percentage of patients in a study arm who develop serious non-COVID-19 viral, bacterial, or fungal infections (e.g., bloodstream infection, hospital-acquired pneumonia, ventilator-associated pneumonia, opportunistic infection) following randomization and up to the 28-day assessment of overall survival.
Measure: Safety: Rate of Secondary Infection Time: 28 daysBeyond supportive care, there are currently no proven treatment options for coronavirus disease (COVID-19) and related pneumonia, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Investigators have seen recently from experience in Western countries with best health care systems that pandemics cannot be managed in hospitals. Investigators have seen ICUs crowded to capacity, healthcare workers being exposed and going to quarantine or dying after exposure to large doses of viral inoculums. Investigators recommend that institutions should register for Clinical trials and consider emergency use of TPE. In Pandemics, time is of essence to avoid mortality by intervening early with available evidence, preferably as part of clinical trial.Since the outbreak of corona virus disease (COVID-19), main treatment modalities have been antivirals, interferons, glucocorticoids, anti-coagulants and supportive treatment in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline / chloroquine sulphate, azithromycin, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small and remain in the experimental phase with currently no effective / specific antiviral with robust scientific evidence as regards the mortality reduction in COVID-19.In an attempt to treat COVID-19, investigator will use different investigational treatment either alone or in combination to see mortality and morbidity benefit on the basis of limitted evidence available so far. These investigational modalities include Therapeutic plasma exchange (TPE), Convalescent Plasma (CP), Remdesivir, Tocilizumab and Mesenchymal stem cell (MSC) therapy in addition to standard supportive treatment.
Description: death or recovery
Measure: survival Time: 28 daysDescription: duration in days
Measure: duration of hospitalization Time: 28 daysDescription: duration in days to normalize symptoms and laboratory parameters
Measure: Time to resolution of cytokine release storm Time: 28 daysDescription: Time in days to turn PCR negative
Measure: Time of viral clearance Time: 45 daysDescription: incidence of Post Covid lung fibrosis
Measure: Complications Time: 90 daysrandomized controlled trial comparing survival benefit of Tocilizumab therapy with dexamethasone in patients with severe COVID 19
Description: survival 14 days from admission date
Measure: Proportion of participants with Overall Survival at 14 days Time: 14 daysDescription: Change in Fio2/Pao2
Measure: Fio2/Pao2 Time: 2 daysThe most accepted description of severe COVID-19 disease is development and over production of pro-inflammatory cytokines. Autopsy studies have been done on COVID-19 patients proved that severe disease is resulted due to deviant host-immune response and cytokine storm. Elevated inflammatory biomarkers like C-Reactive protein (CRP) and pro-inflammatory cytokines shown to be higher in severe disease of COVID-19. Several studies on severe COVID-19 have revealed raised levels of plasma cytokines like IL-6, IL-2, IL-10, Gamma interferon (INF), Tumor necrosis factor Alpha TNF. The Cytokines release syndrome (CRS) is a hyperinflammatory deadly syndrome characterized by release of uncontrolled immune system activation which is responsible for multi-organ failure. It has the main role in ARDS due to SARS-CoV-2 virus which binds to alveolar epithelium and resulting in IL-6 release that is responsible for increase alveolar-epithelium permeability. In many studies it has been observed that IL-6 have played a main role in CRS induction. Previous experiences from hyperinflammatory and cytokine storm syndromes recommends that early involvement of inhibiting CRS is essential to prevent lethal tissue damage and poor clinical outcome. In this scenario the judgement of clinical specialist who are suggesting that evidence of CRS can be cured with glucocorticoids, I/V immunoglobulin and anti-cytokine therapy cannot be ignored.
Description: Clinical improvement of COVID-19 patients by Tocillzumab The number of intubated patients. The number of patients with death.
Measure: Clinical response after administration Time: 10 daysDescription: Overall survival of COVID-19 patients after drug administration.
Measure: Clinical response to treatment Time: 15 daysDescription: Number of days of hospital admission either in ICU or HDUs till date of discharge
Measure: Duration of hospitalization Time: 15 daysDescription: Mortality rate
Measure: Clinical outcome of the treatment Time: 15 daysDescription: Duration of increased supplemental oxygen requirement from baseline
Measure: Supplemental Oxygen Requirement from Baseline Time: 15 daysThis single center study is an investigator-driven randomized controlled parallel group open-label clinical trial designed to evaluate whether anti-IL-6 antibody tocilizumab (TCZ) can slow the decline in graft function in kidney transplant recipients with chronic antibody-mediated rejection (cAMR). A total of 64 recipients will be allocated to receive either TCZ (n=32) added to the standard of care (SOC) or SOC alone (n=32) for a period of 24 months. Patients will be followed for an additional 12 months. Protocol kidney graft biopsies will be performed at baseline, at 12 and 24 months. The primary outcome is the prevention of decline in graft function as assessed by estimated glomerular filtration rate (eGFR).
Description: Comparison of eGFR decline from baseline at 24 months after start of treatment in the two arms. The eGFR will be assessed by measured creatinine values using CKD-EPI formula in mL/min/1.73m2. CKD-EPI formula is based on age, sex, ethnicity, and serum creatinine and eGFR values are calculated as follows: GFR in mL/min per 1.73 m^2 = 141 x min (SerumCr/k; 1)^a x max(SerumCr/k; 1)^(-1.209) x 0.993^age x F x B, where k=0.7 for female (else=0.9); a=-0.329 for female (else=-0.411), F=1.018 for female (else=1), B=1.159 for black (else=1), min/max=minimum/maximum of listed values.
Measure: Change from baseline in eGFR at 24 months Time: Baseline and 24 monthsDescription: Change in DSA from baseline based on luminex assessments every 12 months
Measure: Change in Donor-specific anti-HLA antibodies (DSA) Time: baseline and up to 36 monthsDescription: Assessments of incidence of any side effects including infectious complications associated with TCZ therapy
Measure: Incidence of adverse and serious events related to TCZ treatment Time: up to 25 monthsDescription: Histologic changes at 12 and 24 months will be compared with those in the baseline biopsies. If the criteria for cAMR are no longer fulfilled in the follow-up biopsies, response to therapy is assumed. The response will be assessed as a yes/no categorical variable. In all biopsies, which still meet the required criteria for cAMR, means of individual Banff lesion scores will be compared between the baseline biopsy and the 12- and 24-months biopsies
Measure: Histologic changes in protocol biopsy Time: baseline and up to 24 monthsDescription: Assessed by urine albumin creatinine ratio (UACR) at baseline and every 12 months
Measure: Changes in proteinuria Time: baseline and up to 36 monthsDescription: Changes from baseline in renal function as assessed by mGFR using iohexol clearance
Measure: Renal function assessed by measured GFR (mGFR) Time: baseline and up to 36 monthsDescription: Changes from baseline in renal function at 12 and 36 months after start of treatment, as assessed by eGFR (CKD-EPI)
Measure: Renal function assessed by eGFR Time: baseline and up to 36 monthsDescription: Incidence of patient survival at 12, 24 and 36 months after start of treatment
Measure: Patient survival Time: up to 36 monthsDescription: Incidence of death-censored graft survival at 12, 24 and 36 months after start of treatment
Measure: Death-censored graft survival Time: up to 36 monthsDescription: Assessed using a validated self-reported questionnaires at baseline and every 12 months
Measure: Possible change in experienced transplant-specific well-being and symptom burden Time: upto 36 monthsDescription: Assessed using a validated self-reported questionnaires at baseline and every 12 months
Measure: Possible change in experienced perceived threat of the risk of graft rejection Time: upto 36 monthsDescription: Assessed using a validated self-reported questionnaires at baseline and every 12 months
Measure: Possible change in adherence to immunosuppressive medications Time: upto 36 monthsThe COVID-19 infection primarily manifests itself as a respiratory tract infection, although new evidence indicates that this disease has systemic involvement involving multiple systems including the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic and immune systems. Recent studies have shown that in its pathophysiology, inflammation and thrombogenesis predominate, especially in the severe forms of COVID-19. Thus, the investigators hypothesized that the use of heparin and tocilizumab could potencially reduce inflammation and thrombogenesis in patients with severe COVID-19 infection, improving patients outcomes and survival.
Description: Proportion of patients with clinical improvement in 30 days, defined by hospital discharge or a reduction of at least 2 points compared to baseline on the ordinal scale recommended by the World Health Organization: Not hospitalized, with no limitations on activities; Not hospitalized, but limited to activities; Hospitalized, with no need for supplemental oxygen; Hospitalized, needing supplemental oxygen; Hospitalized, requiring high flow oxygen therapy, non-invasive mechanical ventilation or both; Hospitalized, requiring ECMO, invasive mechanical ventilation or both; Death.
Measure: Proportion of patients with clinical improvement Time: 30 daysDescription: Number of days in hospital and ICU
Measure: Hospital and ICU length of stay; Time: 30 daysDescription: Rate and Time of invasive mechanical ventilation
Measure: Duration of invasive mechanical ventilation Time: 30 daysDescription: Time of use of vasopressors
Measure: Duration of vasopressor use Time: 30 daysDescription: Renal failure by AKIN criteria in 30 days
Measure: Renal failure by AKIN criteria Time: 30 daysDescription: Myocardial injury; Acute myocardial infarction; Cardiogenic shock; arrhythmias; Myocarditis; Pericarditis; Ventricular dysfunction.
Measure: Incidence of cardiovascular complications Time: 30 daysDescription: Deep vein thrombosis and pulmonary embolism
Measure: Incidence of venous thromboembolism Time: 30 daysDescription: Mortality rate
Measure: Mortality Time: 30, 60 and 90 daysAlphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on December 13, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
Drug Reports MeSH Reports HPO Reports