Covid 19 Research using Clinical Trials (Home Page)
BaricitinibWiki
Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation
Correlated Drug Terms (15)
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug2043 | PTI-125, 100 mg tablet Wiki | 0.38 |
| drug2836 | Technology based social interactions Wiki | 0.38 |
| drug2583 | Self-management booklet (SWitCh: Stay well during COVID-19) Wiki | 0.38 |
| drug1895 | No research related technology based social interactions Wiki | 0.38 |
| drug1148 | GENUS device (Active Settings) Wiki | 0.38 |
| drug668 | Chronic Hypersensitivity Pneumonitis Health Related Quality of Life Survey Instrument Wiki | 0.38 |
| drug893 | DigiVis visual acuity app Wiki | 0.38 |
| drug1149 | GENUS device (Sham Settings) Wiki | 0.38 |
| drug2374 | Ravulizumab Wiki | 0.27 |
| drug2955 | Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit Wiki | 0.27 |
| drug2131 | Placebo Administration Wiki | 0.27 |
| drug2707 | Standard of care Wiki | 0.09 |
| drug2413 | Remdesivir Wiki | 0.09 |
| drug2122 | Placebo Wiki | 0.04 |
| drug1284 | Hydroxychloroquine Wiki | 0.04 |
Correlated MeSH Terms (13)
| Name (Synonyms) | Correlation | |
|---|---|---|
| D000544 | Alzheimer Disease NIH | 0.76 |
| D000542 | Alveolitis, Extrinsic Allergic NIH | 0.38 |
| D000550 | Amblyopia NIH | 0.38 |
| D008569 | Memory Disorders NIH | 0.38 |
| D014786 | Vision Disorders NIH | 0.27 |
| D015354 | Vision, Low NIH | 0.27 |
| D060825 | Cognitive Dysfunction NIH | 0.24 |
| D006967 | Hypersensitivity, NIH | 0.17 |
| D017563 | Lung Diseases, Interstitial NIH | 0.11 |
| D008171 | Lung Diseases, NIH | 0.09 |
| D011014 | Pneumonia NIH | 0.04 |
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.02 |
| D018352 | Coronavirus Infections NIH | 0.01 |
Correlated HPO Terms (11)
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0002511 | Alzheimer disease HPO | 0.76 |
| HP:0000646 | Amblyopia HPO | 0.38 |
| HP:0002354 | Memory impairment HPO | 0.38 |
| HP:0006516 | Hypersensitivity pneumonitis HPO | 0.38 |
| HP:0000505 | Visual impairment HPO | 0.27 |
| HP:0012047 | Hemeralopia HPO | 0.27 |
| HP:0001268 | Mental deterioration HPO | 0.24 |
| HP:0012393 | Allergy HPO | 0.17 |
| HP:0006515 | Interstitial pneumonitis HPO | 0.11 |
| HP:0002088 | Abnormal lung morphology HPO | 0.09 |
| HP:0002090 | Pneumonia HPO | 0.04 |
There are 7 clinical trials
Clinical Trials
1 Baricitinib Combined With Antiviral Therapy in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study
There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. Baricitinib, an anti-Janus kinase inhibitor (anti-JAK) acting against JAK1 and JAK2. The drug was found capable to reduce or interrupt the passage of the virus into target cells, and to inhibit the JAK1- and JAK2-mediated cytokine release. The drug was licensed for the treatment of rheumatoid arthritis at the daily dose of 4 mg/orally, with excellent results in terms of clinical response and a good safety profile. Since baricitinib does not interact with antivirals due to its prevalent renal elimination, it may be used in combination.The evidence on the advantageous action of baricitinib on viral entry and cytokine outbreak constituted the rationale to perform a trial on patients with mild to moderate COVID-19 infection receiving baricitinib combined with antiviral therapy.
NCT04320277 Pharmacological Action Drug: Baricitinib
Primary Outcomes
Description: The percentage of ICU admission in patients and controls will be compared for statistical difference
Measure: The percentage of patients requiring transfer to ICU as compared with the rate of transfers observed in controls. Time: 2 weeksSecondary Outcomes
Description: CRP values will be evaluated for prediction of disease worsening.
Measure: The percentage of patients achieving the remission; CRP, IL-6 and TNFα values at baseline and during the treatment course; the number of AEs. Time: 2 weeks2 Safety and Efficacy of Baricitinib for COVID-19
This study plans to learn more about the effects of a medicine called baricitinib on the progression of COVID-19 (coronavirus disease of 2019), the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Baricitinib is FDA-approved for the treatment of rheumatoid arthritis, an autoimmune condition. This study intends to define the impact of baricitinib on the severity and progression of COVID-19. This drug might to lower the hyperinflammation caused by the virus, which would prevent damage to the lungs and possibly other organs. The study will recruit patients who have been diagnosed with COVID-19. The goal is to recruit 80 patients.
NCT04340232 COVID-19 Drug: Baricitinib
Primary Outcomes
Description: Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. AEs will be collected and graded daily and cumulative incidence will be reported.
Measure: Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs) Time: Day 0 (screening) through Day 29Description: Description: An SAE is defined as an AE that is life-threatening or results in death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. SAEs will be collected and graded daily and cumulative incidence will be reported.
Measure: Phase 2: Cumulative incidence of serious adverse events (SAEs) Time: Day 0 (screening) through Day 29Description: Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as standard of care (SOC). Mean changes from baseline to Day 15 will be reported.
Measure: Phase 2: Changes in white blood cell count (CBC) through Day 15 Time: Day 1 to Day 15Measure: Phase 2: Changes in hemoglobin through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in platelets through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in creatinine through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in glucose through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in prothrombin time (PT) through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in total bilirubin through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in ALT through Day 15 Time: Day 1 to Day 15
Measure: Phase 2: Changes in AST through Day 15 Time: Day 1 to Day 15
Description: Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.
Measure: Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS) Time: Day through Day 29 or hospital discharge, whichever is firstMeasure: Phase 2: Changes in hemoglobin through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in platelets through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in creatinine through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in glucose through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in prothrombin time (PT) though End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in total bilirubin through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in ALT through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 2: Changes in AST through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Description: The 8-point ordinal scale described below, where a lower score indicates a worse outcome, will be performed daily or as recommended by participant's physician as SOC. The percent of participants scored at each severity will be reported on Day 15. The 8-point ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities
Measure: Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at Day 15 Time: Day 15Secondary Outcomes
Description: The 8-point ordinal scale described above will be assessed using MR data collected as SOC or follow-up phone call on Day 29, where a lower score indicates a worse outcome. Mean changes from baseline to Day 29 will be reported.
Measure: Phase 2: Change in the 8-point ordinal scale Time: Day 1 to Day 29Description: The NEWS is a cumulative score (range: 0 - 20) based on 7 clinical parameters as depicted below and discriminates patients at risk of poor outcomes. A higher score indicates a higher risk. The assessment will be calculated daily using MR data collected as SOC. Mean changes from baseline to End of Study (Day 29 or discharge) will be reported.
Measure: Phase 2: Change in National Early Warning Score (NEWS) Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: The 8-point ordinal scale described above will be assessed daily using MR data collected as SOC or follow-up phone call, where a lower score indicates a worse outcome. Mean changes from baseline to Day 29 will be reported.
Measure: Phase 3: Change in the 8-point ordinal scale Time: Day 1 to Day 29Description: The NEWS is a cumulative score (range: 0 - 20) based on 7 clinical parameters as depicted below and discriminates patients at risk of poor outcomes. A higher score indicates a higher risk. The assessment will be calculated daily using MR data collected as SOC. Mean changes from baseline to End of Study (Day 29 or discharge) will be reported.
Measure: Phase 3: Change in National Early Warning Score (NEWS) Time: Day 1 to Day 29 or hospital discharge, whichever is firstDescription: The 8-point ordinal scale described above will be assessed daily using MR data collected as SOC, where a lower score indicates a worse outcome. Mean time in days to a one-category improvement will be reported.
Measure: Phase 3: Time to an improvement of one category using the 8-point ordinal scale Time: Day 1 to Day 29 or hospital discharge, whichever is firstDescription: The 8-point ordinal scale described above will be assessed daily, where a lower score indicates a worse outcome. Mean time in days to a two-category improvement will be reported.
Measure: Phase 3: Time to an improvement of two categories using the 8-point ordinal scale Time: Day 1 to Day 29 or hospital discharge, whichever is firstDescription: The NEWS will be calculated daily. Mean time in days to achieve a score of ≤2 and maintain this score for at least 24 hours OR to be discharged from the hospital, whichever occurs first, will be reported. A higher score indicates a higher risk. End of study is defined as day 29 or discharge, whichever occurs first.
Measure: Phase 3: Time to discharge or to a NEWS ≤2 and maintained for 24 hours, whichever occurs first Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. AEs will be collected and graded daily and cumulative incidence will be reported.
Measure: Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs) Time: Day 0 (screening) through Day 29Description: An SAE is defined as an AE that is life-threatening or results in death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. SAEs will be collected and graded daily and cumulative incidence will be reported.
Measure: Phase 3: Cumulative incidence of serious adverse events (SAEs) Time: Day 0 (screening) through Day 29Description: The mean duration of hospitalization will be reported, measured in days.
Measure: Phase 3: Duration of hospitalization Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: The mean duration of new oxygen use will be reported, measured in days.
Measure: Phase 3: Duration of new oxygen use Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: The mean duration of new ventilator or ECMO use will be reported, measured in days.
Measure: Phase 3: Duration of new ventilator or ECMO use Time: Day 1 to Day 29 or hospital discharge, whichever is firstDescription: The incidence of interruption of baricitinib treatment, along with mean duration and reasons for the interruptions, will be reported.
Measure: Phase 3: Incidence of discontinuation or temporary suspension of drug for any reason Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: The incidence of new oxygen use will be reported.
Measure: Phase 3: Incidence of new oxygen use Time: Day 1 to Day 29 or hospital discharge, whichever is firstDescription: The incidence of new ventilator or ECMO use will be reported.
Measure: Phase 3: Incidence of new ventilator use Time: Day 1 to Day 29 or hospital discharge, whichever is firstDescription: The mean number of days patients are free from use of oxygen will be reported.
Measure: Phase 3: Number of oxygen free days Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: The mean number of days patients are free from use of a ventilator or ECMO will be reported.
Measure: Phase 3: Number of ventilator or ECMO free days Time: Day 1 through Day 29 or hospital discharge, whichever is firstDescription: The rate of participant death from Day 1 through Day 15 will be reported.
Measure: Phase 3: 14 day mortality rate Time: Day 1 through Day 15Description: The rate of participant death from Day 1 through Day 29 will be reported.
Measure: Phase 3: 28 day mortality rate Time: Day 1 through Day 29Measure: Phase 3: Changes in white blood cell count (CBC) through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in hemoglobin through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in platelets through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in creatinine through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in glucose through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in prothrombin time (PT) through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in total bilirubin through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in ALT through Day 15 Time: Day 1 to Day 15
Measure: Phase 3: Changes in AST through Day 15 Time: Day 1 to Day 15
Description: Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.
Measure: Phase 3: Changes in white blood cell count (CBC) through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is firstMeasure: Phase 3: Changes in hemoglobin through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in platelets through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in creatinine through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in glucose through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in prothrombin time (PT) though End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in total bilirubin through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in ALT through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
Measure: Phase 3: Changes in AST through End of Study (EOS) Time: Day 1 through Day 29 or hospital discharge, whichever is first
3 A Phase II Randomized Double-Blind Trial of Baricitinib or Placebo Combined With Antiviral Therapy in Patients With Moderate and Severe COVID-19
This phase II trial studies the effect of baricitinib in combination with antiviral therapy for the treatment of patients with moderate or severe coronavirus disease-2019 (COVID-19). Treatment with antiviral medications such as hydroxychloroquine, lopinavir/ritonavir, and/or remdesivir may act against infection caused by the virus responsible for COVID-19. Baricitinib may reduce lung inflammation. Giving baricitinib in combination with antiviral therapy may reduce the risk of the disease from getting worse and may help prevent the need for being placed on a ventilator should the disease worsen compared to antiviral therapy alone.
NCT04373044 Symptomatic COVID-19 Infection Laboratory-Confirmed Drug: Baricitinib Drug: Hydroxychloroquine Drug: Placebo Administration MeSH:Laboratory Infection
Primary Outcomes
Description: Descriptive statistics, including means, standard deviations, and ranges for continuous variables, as well as percentages and frequencies for categorical variables, will be provided to describe all the clinical findings in a cohort of symptomatic coronavirus disease 2019 (COVID-19)-infected subjects. The collected data will also be graphically presented in boxplots, histograms, and scatter plots. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity, will be made. Group comparisons will be made using either the parametric tests such as t-test and analysis of variance (ANOVA), or the non-parametric statistical method such as Wilcoxon and Kruskal-Wallis tests for continuous variable and Chi-square test for categorical variables. Point estimates, along with the corresponding p-values and 95% confidence intervals will be reported.
Measure: Proportion of patients requiring invasive mechanical ventilation or dying Time: Up to 14 daysSecondary Outcomes
Description: Body temperature will be measured in degrees Fahrenheit using an automated thermometer.
Measure: Identification of clinical features (vitals signs - body temperature) Time: Up to 28 daysDescription: Respiratory rate in times/minute
Measure: Identification of clinical features (vital signs - respiratory rate) Time: Up to 28 daysDescription: Heart rate in beats/minute
Measure: Identification of clinical features (vital signs - heart rate) Time: Up to 28 daysDescription: Blood pressure in mmHg
Measure: Identification of clinical features (vital signs - blood pressure) Time: Up to 28 daysDescription: Chest X-ray or pulmonary computed tomography (CT) will be performed
Measure: Identification of clinical features (Imaging) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - White Blood Count) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - Absolute Lymphocyte Count) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - Hemoglobin) Time: Up to 28 daysDescription: Assessment via standard blood chemistry and metabolic panel
Measure: Identification of clinical features (Lab - Creatinine) Time: Up to 28 daysDescription: CRP is assessed by routinely used determination of CRP.
Measure: Identification of biomarkers (C-reactive protein) Time: Up to 14 daysDescription: IL-6 levels will be assessed using commercial ELISA method
Measure: Identification of biomarkers (Interleukin-6) Time: Up to 14 daysDescription: Tumor Necrosis Factor-alpha as measured in hospital laboratory
Measure: Identification of biomarkers (Tumor Necrosis Factor-alpha) Time: Up to 14 daysDescription: Descriptive statistics, including means, standard deviations, and ranges for continuous variables, as well as percentages and frequencies for categorical variables, will be provided to describe all the clinical findings in a cohort of symptomatic COVID-19-infected subjects. The collected data will also be graphically presented in boxplots, histograms, and scatter plots. Investigations for outliers and assumptions for statistical analysis, e.g., normality and homoscedasticity, will be made. Group comparisons will be made using either the parametric tests such as t-test and ANOVA, or the non-parametric statistical method such as Wilcoxon and Kruskal-Wallis tests for continuous variable and Chi-square test for categorical variables. Point estimates, along with the corresponding p-values and 95% confidence intervals will be reported.
Measure: Identification of adverse events Time: Up to 14 daysOther Outcomes
Measure: Measurement of COVID19 viral burden Time: Up to 14 days4 mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Repurposed Drugs (TACTIC-R)
TACTIC-R is a randomised, parallel arm, open-label platform trial for investigating potential treatment for COVID-19 disease. While SARS-CoV infection evades detection by the immune system in the first 24 hours of infection, it ultimately produces a massive immune system response in the subgroup of people who develop severe complications. Most tissue damage following infection with COVID19 appears to be due to a later, exaggerated, host immune response. This leads to lung and sometimes multi-organ damage. Most people who develop these severe complications still have virus present in their respiratory tract at the time-point when the disease starts to evolve. Immune modulation in the presence of active infection has potential to cause more harm than benefit. Safety considerations when studying immune modulation strategies are paramount. Therefore, this study proposes to assess the efficacy of immunomodulatory agents that target dysregulated immune response that drive the severe lung, and other organ, damage. The medications investigated for efficacy in this trial are Baricitinib and Ravulizumab.
NCT04390464 COVID19 Drug: Ravulizumab Drug: Baricitinib Other: Standard of care
Primary Outcomes
Description: Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73m^2), haemofiltration or dialysis
Measure: Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure Time: up to Day 14Secondary Outcomes
Description: The clinical status of the patients is assessed using 7-point ordinal scale as follows: 1 = Death, 2 = Mechanical ventilation, 3 = Non-invasive or high flow oxygen, 4 = Low flow oxygen, 5 = Hospitalised - no oxygen, 6 = Discharged - normal activities not resumed, 7 = Discharged - normal activities resumed
Measure: Change in clinical status as assessed on 7-point ordinal scale compared to baseline Time: 14 daysDescription: The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: venous thromboembolism, new infections requiring antimicrobials
Measure: Proportion of patients with adverse events of special interest in each treatment arm Time: 14 daysDescription: The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days
Measure: Time to Sp02 >94% on room air Time: 14 daysDescription: The amount of time between a patient's first positive SARS-CoV2 PCR test and a patient's first negative SARS-CoV2 PCR test, measured in days
Measure: Time to first negative SARS-CoV2 PCR Time: 14 daysDescription: The duration of oxygen therapy given to a patient, measured in days
Measure: Duration of oxygen therapy Time: 14 daysDescription: The duration of hospitalisation of a patient, measured in days
Measure: Duration of hospitalisation Time: 14 daysDescription: The number of deaths recorded at 28 days irrespective of the cause
Measure: All cause mortality at day 28 Time: 28 DaysDescription: The time to clinical improvement for a patient, defined as: >2 point improvement from Day 1 on the 7-point ordinal scale, measured in days
Measure: Time to clinical improvement Time: 14 days5 A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia
The objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia. This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.
NCT04399798 Corona Virus Infection Drug: Baricitinib MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia
Primary Outcomes
Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria) Time: 8 days
Description: Absence of death within 8 days from enrollment
Measure: Response to treatment: survival Time: 8 days
Secondary Outcomes
Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days Time: 8 days
Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days Time: 15 days
Description: To quantify mortality within 8 and 15 days
Measure: Mortality Time: 8 days and 15 days
Description: SpO2 will be assessed with the median and 25th-75th percentiles
Measure: Peripheral capillary oxygen saturation (SpO2) Time: 8 days; 15 days
Description: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2) Time: 8 days; 15 days
Description: Number of patients over the number of patients enrolled
Measure: To assess the rate of patients admitted to the intensive care unit Time: 8 days; 15 days
Description: Median number of days and 25th-75th percentiles
Measure: To measure the length of hospital stay Time: 8 days; 15 days
Description: To quantify 28-day mortality
Measure: 28-day mortality Time: 28 days
Description: Number of patients readmitted over the number patients enrolled
Measure: To quantify the rate of re-admission within 28 days Time: 28 days
Description: Number, type, and severity of adverse events
Measure: To quantify the cumulative incidence and severity of adverse events Time: 28 days
Description: Serial serum assessments from baseline up to 15 days
Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels; Time: 15 days
Description: Serial serum assessments from baseline up to 15 days
Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels Time: 15 days
Description: Serial assessments from baseline up to 15 days for viral load persistence
Measure: Viral load analyses Time: 15 days
6 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-2)
Primary Outcomes
Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria) Time: 8 daysDescription: Absence of death within 8 days from enrollment
Measure: Response to treatment: survival Time: 8 daysSecondary Outcomes
Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days Time: 8 daysDescription: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days Time: 15 daysDescription: To quantify mortality within 8 and 15 days
Measure: Mortality Time: 8 days and 15 daysDescription: SpO2 will be assessed with the median and 25th-75th percentiles
Measure: Peripheral capillary oxygen saturation (SpO2) Time: 8 days; 15 daysDescription: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2) Time: 8 days; 15 daysDescription: Number of patients over the number of patients enrolled
Measure: To assess the rate of patients admitted to the intensive care unit Time: 8 days; 15 daysDescription: Median number of days and 25th-75th percentiles
Measure: To measure the length of hospital stay Time: 8 days; 15 daysDescription: To quantify 28-day mortality
Measure: 28-day mortality Time: 28 daysDescription: Number of patients readmitted over the number patients enrolled
Measure: To quantify the rate of re-admission within 28 days Time: 28 daysDescription: Number, type, and severity of adverse events
Measure: To quantify the cumulative incidence and severity of adverse events Time: 28 daysDescription: Serial serum assessments from baseline up to 15 days
Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels; Time: 15 daysDescription: Serial serum assessments from baseline up to 15 days
Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels Time: 15 daysDescription: Serial assessments from baseline up to 15 days for viral load persistence
Measure: Viral load analyses Time: 15 daysACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.
NCT04401579 COVID-19 Other: Placebo Drug: Remdesivir Drug: Baricitinib
Primary Outcomes
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.
Measure: Time to recovery Time: Day 1 through Day 29Secondary Outcomes
Measure: Change from baseline in alanine transaminase (ALT) Time: Day 1 through Day 29Measure: Change from baseline in aspartate transaminase (AST) Time: Day 1 through Day 29
Measure: Change from baseline in creatinine Time: Day 1 through Day 29
Measure: Change from baseline in glucose Time: Day 1 through Day 29
Measure: Change from baseline in hemoglobin Time: Day 1 through Day 29
Measure: Change from baseline in platelets Time: Day 1 through Day 29
Description: PT reported as international normalized ratio (INR).
Measure: Change from baseline in prothrombin time (PT) Time: Day 1 through Day 29Measure: Change from baseline in total bilirubin Time: Day 1 through Day 29
Measure: Change from baseline in white blood cell count (WBC) with differential Time: Day 1 through Day 29
Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Change in National Early Warning Score (NEWS) from baseline Time: Day 1 through Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Cumulative incidence of serious adverse events (SAEs) Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Measured in days
Measure: Duration of oxygen use Time: Day 1 through Day 29Description: For any reason.
Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Measure: Incidence of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29
Measure: Incidence of new oxygen use Time: Day 1 through Day 29
Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29
Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Mean change in the ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Participant's clinical status at Day 15 by ordinal scale Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale Time: Days 3, 5, 8, 11, 22, and 29Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 28-day mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29Measure: Change from baseline in C-reactive protein (CRP) Time: Day 1 through Day 29
Measure: Change from baseline in d-dimer concentration Time: Day 1 through Day 29
7 A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.
NCT04421027 COVID-19 Drug: Baricitinib Drug: Placebo
Primary Outcomes
Description: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including ECMO)
Measure: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including extracorporeal membrane oxygenation [ECMO]) Time: Day 1 to Day 28Secondary Outcomes
Description: The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.
Measure: Percentage of Participants with at Least 1-Point Improvement on NIAID-OS or Live Discharge from Hospital Time: Day 10Description: Number of Ventilator-Free Days
Measure: Number of Ventilator-Free Days Time: Day 1 to Day 28Description: Recovery assessed by the NIAID-OS.
Measure: Time to Recovery Time: Day 1 to Day 28Description: Overall Improvement on the NIAID-OS
Measure: Overall Improvement on the NIAID-OS Time: Day 1 to Day 28Description: Duration of Hospitalization
Measure: Duration of Hospitalization Time: Day 1 to Day 28Description: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline
Measure: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline Time: Day 10Description: Mortality
Measure: Mortality Time: Day 1 to Day 28Description: Duration of Stay in the ICU in Days
Measure: Duration of Stay in the Intensive Care Unit (ICU) in Days Time: Day 1 to Day 28Description: Time to Clinical Deterioration (one-category increase on the NIAID-OS)
Measure: Time to Clinical Deterioration (one-category increase on the NIAID-OS) Time: Day 1 to Day 28Description: Time to Resolution of Fever, in Participants with Fever at Baseline
Measure: Time to Resolution of Fever, in Participants with Fever at Baseline Time: Day 1 to Day 28Description: The NEWS is used to detect and report changes in illness severity in participants with acute illness. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness
Measure: Mean Change from Baseline on the National Early Warning Score (NEWS) Time: Baseline, Day 1 to Day 28Description: Time to Definitive Extubation
Measure: Time to Definitive Extubation Time: Day 1 to Day 28Description: Time to Independence from Non-Invasive Mechanical Ventilation
Measure: Time to Independence from Non-Invasive Mechanical Ventilation Time: Day 1 to Day 28Description: Time to Independence from Oxygen Therapy in Days
Measure: Time to Independence from Oxygen Therapy in Days Time: Day 1 to Day 28Description: Number of Days with Supplemental Oxygen Use
Measure: Number of Days with Supplemental Oxygen Use Time: Day 1 to Day 28Description: Number of Days of Resting Respiratory Rate <24 Breaths per Minute
Measure: Number of Days of Resting Respiratory Rate <24 Breaths per Minute Time: Day 1 to Day 28