Covid 19 Research using Clinical Trials (Home Page)
AnakinraWiki
Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation
Correlated Drug Terms (30)
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug250 | Ceftriaxone Wiki | 0.38 |
| drug1240 | Web Based Survey Wiki | 0.38 |
| drug442 | Fixed-duration Hydrocortisone Wiki | 0.38 |
| drug512 | Hydroxychloroquine + lopinavir/ritonavir Wiki | 0.38 |
| drug469 | HCQ & AZ Wiki | 0.38 |
| drug1032 | Shock-dependent hydrocortisone Wiki | 0.38 |
| drug592 | Interferon-β1a Wiki | 0.38 |
| drug711 | Moxifloxacin or Levofloxacin Wiki | 0.38 |
| drug675 | Macrolide administered for up to 14 days Wiki | 0.38 |
| drug2 | (Standard of Care) SoC Wiki | 0.38 |
| drug443 | Fixed-duration higher dose Hydrocortisone Wiki | 0.38 |
| drug1416 | trimethoprim/sulfamethoxazole Wiki | 0.38 |
| drug59 | Amoxicillin-clavulanate Wiki | 0.38 |
| drug441 | Five-days oseltamivir Wiki | 0.38 |
| drug249 | Ceftaroline Wiki | 0.38 |
| drug674 | Macrolide administered for 3-5 days Wiki | 0.38 |
| drug848 | Piperacillin-tazobactam Wiki | 0.38 |
| drug403 | Emapalumab Wiki | 0.38 |
| drug1138 | Ten-days oseltamivir Wiki | 0.38 |
| drug775 | Normal saline Wiki | 0.27 |
| drug1033 | Siltuximab Wiki | 0.27 |
| drug1168 | Tocilizumab Wiki | 0.26 |
| drug1211 | Usual Care Wiki | 0.19 |
| drug1012 | Sarilumab Wiki | 0.15 |
| drug650 | Losartan Wiki | 0.14 |
| drug505 | Hydroxychloroquine Wiki | 0.12 |
| drug957 | Remdesivir Wiki | 0.11 |
| drug647 | Lopinavir/ritonavir Wiki | 0.11 |
| drug865 | Placebo oral tablet Wiki | 0.08 |
| drug850 | Placebo Wiki | 0.03 |
Correlated MeSH Terms (11)
| Name (Synonyms) | Correlation | |
|---|---|---|
| D055501 | Macrophage Activation Syndrome NIH | 0.38 |
| D007239 | Infection NIH | 0.14 |
| D003141 | Communicable Diseases NIH | 0.12 |
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.11 |
| D014777 | Virus Diseases NIH | 0.11 |
| D055371 | Acute Lung Injury NIH | 0.10 |
| D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.10 |
| D018352 | Coronavirus Infections NIH | 0.09 |
| D012141 | Respiratory Tract Infections NIH | 0.09 |
| D012128 | Respiratory Distress Syndrome, Adult NIH | 0.08 |
| D011014 | Pneumonia NIH | 0.03 |
Correlated HPO Terms (2)
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0011947 | Respiratory tract infection HPO | 0.09 |
| HP:0002090 | Pneumonia HPO | 0.03 |
There are 7 clinical trials
Clinical Trials
1 Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
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 ofon 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.
NCT02735707 Community-acquired Pneumonia, Influenza, COVID-19 Drug: Fixed-duration Hydrocortisone Drug: Shock-dependent hydrocortisone Drug: Ceftriaxone Drug: Moxifloxacin or Levofloxacin Drug: Piperacillin-tazobactam Drug: Ceftaroline Drug: Amoxicillin-clavulanate Drug: Macrolide administered for 3-5 days Drug: Macrolide administered for up to 14 days Drug: Five-days oseltamivir Drug: Ten-days oseltamivir Drug: Lopinavir/ritonavir Drug: Hydroxychloroquine Drug: Hydroxychloroquine + lopinavir/ritonavir Drug: Interferon-β1a Drug: Anakinra Drug: Fixed-duration higher dose Hydrocortisone Drug: Tocilizumab Drug: Sarilumab MeSH:Pneumonia
HPO:Pneumonia
Primary Outcomes
Measure: All-cause mortality Time: Day 90
Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and outside of ICU Time: Day 21
Secondary Outcomes
Measure: ICU Mortality Time: Day 90
Measure: ICU length of stay Time: Day 90
Measure: Hospital length of stay Time: Day 90
Measure: Ventilator free days Time: Day 28
Measure: Organ failure free days Time: Day 28
Measure: All-cause mortality Time: 6 months
Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 months
Measure: Proportion of intubated patients who receive a tracheostomy Time: Day 28
Description: 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 90
Measure: Readmission to the index ICU during the index hospitalization Time: Day 90
Measure: World Health Organisation 8-point ordinal scale outcome Time: Hospital discharge
Other Outcomes
Description: Antibiotic Domain specific outcome
Measure: Occurrence of multi-resistant organism colonisation/infection Time: Day 90, censored at hospital discharge
Description: Antibiotic Domain specific outcome
Measure: Occurrence clostridium difficile Time: Day 90, censored at hospital discharge
Description: 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 discharge
Description: 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 7
Description: 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 discharge
2 A Phase 2/3, Randomized, Open-label, Parallel Group, 3-arm, Multicenter Study Investigating the Efficacy and Safety of Intravenous Administrations of Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, and Anakinra, an Interleukin-1(IL-1) Receptor Antagonist, Versus Standard of Care, in Reducing Hyper-inflammation and Respiratory Distress in Patients With SARS-CoV-2 Infection.
Primary Outcomes
Measure: All-cause mortality Time: Day 90Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection
Measure: Days alive and outside of ICU Time: Day 21Secondary Outcomes
Measure: ICU Mortality Time: Day 90Measure: ICU length of stay Time: Day 90
Measure: Hospital length of stay Time: Day 90
Measure: Ventilator free days Time: Day 28
Measure: Organ failure free days Time: Day 28
Measure: All-cause mortality Time: 6 months
Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)
Measure: Health-related Quality of life assessment Time: 6 monthsMeasure: Proportion of intubated patients who receive a tracheostomy Time: Day 28
Description: 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 90Measure: Readmission to the index ICU during the index hospitalization Time: Day 90
Measure: World Health Organisation 8-point ordinal scale outcome Time: Hospital discharge
Other Outcomes
Description: 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 dischargeAs shown by the data available, hyper-inflammation, caused by a cytokine storm resulting from an exaggerated response of the immune system to the presence of the virus, is considered to represent one of the most important negative prognostic factor in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to investigate new possibilities to reduce the number of patients requiring mechanical ventilation. This is intended to address the most urgent need to preserve the access to intensive care unit support to the lowest possible number of patients and may potentially reduce mortality.
NCT04324021 SARS-CoV-2 Biological: Emapalumab Biological: Anakinra MeSH:Infection
Primary Outcomes
Description: Defined as the proportion of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)
Measure: Treatment success Time: Up to Day 15Secondary Outcomes
Description: Measured in days
Measure: Time to mechanical ventilation Time: Date of randomization to date of mechanical ventilationDescription: Measured in total score
Measure: Change from baseline in Modified Early Warning system score Time: Baseline, Day 15Description: Measured in percent (%)
Measure: Change from baseline in resting peripheral capillary oxygen saturation (SpO2) Time: Baseline, 3 assessments every Days 4, 7, 10, 13 and 15Description: Measured in percent (%)
Measure: Change from baseline in partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) Time: Baseline, Day 15Description: Measured in local units
Measure: Change of pH in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of carbon dioxide tension (pCO2) in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of oxygen tension (pO2) in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of potassium in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of sodium in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of chloride in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of lactic acid in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of hemoglobin in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in l/min
Measure: Change from baseline in oxygen supplementation Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in scan evaluation: Normal, Abnormal but not clinically significant, Abnormal clinical significant, Not Done
Measure: Change of findings of high-resolution computed tomography (CT) scan of the chest Time: Screening, Day 15Description: Measured in local units
Measure: Change from baseline in Ferritin Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in lactate dehydrogenase (LDH) Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in D-dimers Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in White Blood Cells with differential counts Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Red Blood Counts Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Hemoglobin Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Platelet count Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Fibrinogen Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Complement factors C3/C4 Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Prothrombin time Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Cardiac troponin Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in aspartate aminotransferase (AST) Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in alanine aminotransferase (ALT) Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in total bilirubin levels Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in C-Reactive Protein Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Creatinine Time: Baseline, Days 4, 7, 10, 13 and 15Description: Confirmation of death
Measure: Overall survival Time: Weeks 6 and 10Description: Measured in days
Measure: Time to hospital discharge Time: Weeks 6 and 103 A Prospective, Randomized, Factorial Design, Interventional Study to Compare the Safety and Efficacy of Combinations of Blockade of Interleukin-6 Pathway and Interleukin-1 Pathway to Best Standard of Care in Improving Oxygenation and Short- and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure and Systemic Cytokine Release Syndrome
The 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
NCT04330638 COVID-19 Other: Usual Care Drug: Anakinra Drug: Siltuximab Drug: Tocilizumab
Primary Outcomes
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 15Secondary Outcomes
Description: 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 firstMeasure: Number of days with hypoxia Time: during hospital admission (up to 28 days)
Measure: Number of days of supplemental oxygen use Time: during hospital admission (up to 28 days)
Measure: Time to absence fever for more than 48h without antipyretics Time: during hospital admission (up to 28 days)
Measure: Number of days with fever Time: during hospital admission (up to 28 days)
Measure: Time to halving of CRP levels compared to peak value during trial Time: during hospital admission (up to 28 days)
Measure: Time to halving of ferritin levels compared to peak value during trial Time: during hospital admission (up to 28 days)
Measure: Incidence of AEs (Adverse Events) Time: during hospital admission (up to 28 days)
Measure: Incidence of SAEs (Serious Adverse Events) Time: during hospital admission (up to 28 days)
Measure: Duration of hospital stay Time: during hospital admission (up to 28 days)
Measure: Duration of hospital stay in survivors Time: during hospital admission (up to 28 days)
Description: Clinical sign score: 0( best) - 18 (worse)
Measure: Mean change in clinical sign score between day 1 and day 7 Time: day 1, day 7 or hospital discharge, whichever is firstDescription: Clinical sign score: 0( best) - 18 (worse)
Measure: Mean change in clinical sign score between day 1 and day 15 Time: day 1, day 15 or hospital discharge, whichever is firstDescription: Clinical sign score: 0( best) - 18 (worse)
Measure: Time to clinical sign score <6 maintained for 24h Time: during hospital admission (up to 28 days)Description: 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: NEWS2 score: 0 (best) - 24 (worse)
Measure: Mean change NEWS2 (National Early Warning) score between day 1 and day 7 Time: day 1, day 7 or hospital discharge, whichever is firstDescription: NEWS2 score: 0 (best) - 24 (worse)
Measure: Mean change NEWS2 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 firstMeasure: Incidence of nosocomial bacterial or invasive fungal infection Time: during hospital admission (up to 28 days)
Description: 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)Measure: Time to first use of high-flow oxygen devices, non-invasive or invasive mechanical ventilation in non-ventilated patients Time: during hospital admission (up to 28 days)
Measure: Time to first use of salvage systemic steroids in ventilated patients Time: during hospital admission (up to 28 days)
Measure: Number of ventilator free days Time: during hospital admission (up to 28 days)
Measure: Duration of mechanical ventilation in ventilated patients Time: during hospital admission (up to 28 days)
Measure: Duration of ICU stay in patients that enrolled in trial while already on invasive or non-invasive mechanical ventilation Time: during hospital admission (up to 28 days)
Measure: Time to progression to ARDS in ventilated patients Time: during hospital admission (up to 28 days)
Measure: Time to progression to ARDS in ventilated patients according to IL-1 Time: during hospital admission (up to 28 days)
Measure: Time to progression to ARDS in ventilated patients according to IL-6 Time: during hospital admission (up to 28 days)
Measure: All-cause mortality rate (excluding group that entered during ventilation) Time: during hospital admission (up to 28 days)
Measure: Percentage of patients in clinical status on 6-point Ordinal Scale Time: at 10-20 weeks follow-up
Measure: Incidence of lung function abnormalities Time: at 10-20 weeks follow-up
Measure: Incidence of lung fibrosis on chest CT scan Time: at 10-20 weeks follow-up
Measure: All-cause mortality rate Time: at 10-20 weeks follow-up
4 Efficiency in Management of Organ Dysfunction Associated With Infection by the Novel SARS-CoV-2 Virus (COVID-19) Through a Personalized Immunotherapy Approach: the ESCAPE Clinical Trial
Our 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.
NCT04339712 COVID-19 Virus Diseases Macrophage Activation Syndrome Corona Virus Infection Drug: Anakinra Drug: Tocilizumab MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Macrophage Activation Syndrome Virus Diseases
Primary Outcomes
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 8Secondary Outcomes
Description: 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: Screening5 CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection, Nested In The CORIMUNO-19
The overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the COVIMUNO-19 cohort. Anakinra 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 Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
NCT04341584 Corona Virus Infection Drug: Anakinra MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome
Primary Outcomes
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. 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 Time: 14 daysDescription: 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.
Measure: WHO progression scale ≤ 5 Time: 4 daysDescription: 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) or withdrawal of NIV or high flow (for > 48h), at day 14 Time: 14 daysDescription: Proportion of patients with a decrease of WHO score of at least 1 point at day 4
Measure: Decrease of at least one point in WHO progression scale score Time: 4 daysSecondary Outcomes
Description: 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 daysMeasure: 28-day ventilator free-days Time: 28 days
Description: 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 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 days6 suPAR-guided Anakinra Treatment for Validation of the Risk and Early Management of Severe Respiratory Failure by COVID-19: The SAVE Open-label, Non-randomized Single-arm Trial
In the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure. Also due to the potential co-existing immunodysfunction in the context of SARS-CoV-2 infection patients will also receive trimethoprim/sulfamethoxazole as part of chemoprophylaxis.
NCT04357366 COVID-19 Virus Dis Virus Diseases Corona Virus Infection Lower Respiratory Tract Infection Viral Drug: Anakinra Drug: trimethoprim/sulfamethoxazole MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency Virus Diseases
HPO:Respiratory tract infection
Primary Outcomes
Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.
Measure: The ratio of patients who will not develop serious respiratory failure (SRF) Time: Visit study day 14
Secondary Outcomes
Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database Time: Visit study day 14
Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7
Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14
Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of SOFA score in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7
Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14
Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7
Measure: Change of cytokine production between days 1 and 7 Time: Visit study day 1, visit study day 7
Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7
Measure: Change of plasma inflammatory mediators levels between days 1 and 7 Time: Visit study day 1, visit study day 7
7 Early Identification and Treatment of Cytokine Storm Syndrome in Covid-19
Primary Outcomes
Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.
Measure: The ratio of patients who will not develop serious respiratory failure (SRF) Time: Visit study day 14Secondary Outcomes
Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database Time: Visit study day 14Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of SOFA score in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7
Measure: Change of cytokine production between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7
Measure: Change of plasma inflammatory mediators levels between days 1 and 7 Time: Visit study day 1, visit study day 7This proposal addresses the problem of preventing the very high mortality and morbidity associated with the development of Cytokine Storm Syndrome (CSS) associated respiratory failure in Covid-19 infection.
NCT04362111 Cytokine Storm COVID-19 Drug: Anakinra Drug: Normal saline
Primary Outcomes
Description: Supplemental oxygen requirement to maintain oxygen saturation >90% stable or decreased without escalation of respiratory measures (addition of CPAP, initiation of mechanical ventilation)
Measure: No increase in oxygen requirement and no increase in respiratory support measures Time: 48 hoursSecondary Outcomes
Description: 25% decrease in noted baseline elevations of serum ferritin, LDH, CRP, and d-dimer.
Measure: Improvement in Cytokine Storm markers Time: 72 hoursDescription: Subjects discharged from hospital without the need for mechanical ventilation
Measure: No requirement for mechanical ventilation Time: Day 5 (120 hours)