CovidResearchTrials by Shray Alag


CovidResearchTrials Covid 19 Research using Clinical Trials (Home Page)


Standard of careWiki

Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (24)


Name (Synonyms) Correlation
drug61 Anakinra alone (stages 2b/3) Wiki 0.30
drug342 Dapagliflozin Wiki 0.30
drug57 Ambrisentan Wiki 0.30
drug894 Prazosin Wiki 0.30
drug388 EDP1815 Wiki 0.30
drug62 Anakinra and Ruxolitinib (overcome stage 3) Wiki 0.30
drug695 Mesenchymal cells Wiki 0.30
drug265 Chloroquine analog (GNS651) Wiki 0.30
drug691 Melphalan Wiki 0.30
drug451 GO2 PEEP MOUTHPIECE Wiki 0.30
drug1116 TAK-981 Wiki 0.30
drug804 Otilimab Wiki 0.30
drug780 Observation of patients with known, suspected, or at risk for COVID-19 infection Wiki 0.30
drug302 Continuous renal replacement therapy Wiki 0.30
drug759 Nivolumab Wiki 0.21
drug586 Interferon Beta-1A Wiki 0.17
drug1168 Tocilizumab Wiki 0.14
drug650 Losartan Wiki 0.11
drug977 Ruxolitinib Wiki 0.11
drug957 Remdesivir Wiki 0.09
drug647 Lopinavir/ritonavir Wiki 0.09
drug850 Placebo Wiki 0.08
drug505 Hydroxychloroquine Wiki 0.07
drug108 Azithromycin Wiki 0.06

Correlated MeSH Terms (15)


Name (Synonyms) Correlation
D009362 Neoplasm Metastasis NIH 0.30
D053120 Respiratory Aspiration NIH 0.15
D019337 Hematologic Neoplasms NIH 0.13
D007249 Inflammation NIH 0.10
D009369 Neoplasms, NIH 0.09
D018352 Coronavirus Infections NIH 0.07
D007239 Infection NIH 0.06
D003141 Communicable Diseases NIH 0.06
D045169 Severe Acute Respiratory Syndrome NIH 0.05
D011024 Pneumonia, Viral NIH 0.04
D013577 Syndrome NIH 0.04
D055371 Acute Lung Injury NIH 0.04
D012127 Respiratory Distress Syndrome, Newborn NIH 0.04
D012128 Respiratory Distress Syndrome, Adult NIH 0.03
D011014 Pneumonia NIH 0.02

Correlated HPO Terms (3)


Name (Synonyms) Correlation
HP:0001909 Leukemia HPO 0.12
HP:0002664 Neoplasm HPO 0.09
HP:0002090 Pneumonia HPO 0.02

There are 11 clinical trials

Clinical Trials


1 An Open Label, Dose-Escalation, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TAK-981 in Adult Patients With Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies and in a Subset With Coronavirus Disease 2019

The primary objective of this study is to evaluate the safety and tolerability of TAK-981 as a single agent in participants with advanced or metastatic solid tumors and lymphomas in dose escalation and cancer treatment expansions, and to assess change in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load within 8 days of TAK-981 administration in COVID expansion.

NCT03648372 Neoplasms Lymphoma Hematologic Neoplasms Coronavirus Disease Drug: TAK-981 Drug: Standard of care
MeSH:Coronavirus Infections Hematologic Neoplasms Neoplasms
HPO:Hematological neoplasm Leukemia Neoplasm

Primary Outcomes

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)

Time: Up to 36 months

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Dose Limiting Toxicities (DLTs)

Time: Up to 36 months

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With one or More Serious Adverse Events (SAEs)

Time: Up to 36 months

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations

Time: Up to 36 months

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs

Time: Up to 36 months

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Clinically Significant Laboratory Values

Time: Up to 36 months

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Clinically Significant Vital Sign Measurements

Time: Up to 36 months

Description: CRS will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants who Experience Cytokine Release Syndrome CRS)

Time: Up to 36 months

Measure: COVID-19 Expansion: Number of Participants With >=2 log Reduction From Baseline in Viral Load or Below Level of Detection (Negative) in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

Secondary Outcomes

Measure: Dose Escalation and Cancer Treatment Expansions, Cmax: Maximum Observed Plasma Concentration for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length is equal to [=] 21 days)

Measure: Dose Escalation and Cancer Treatment Expansions, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

Measure: Dose Escalation and Cancer Treatment Expansions, AUCt: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

Measure: Dose Escalation and Cancer Treatment Expansions, AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

Measure: Dose Escalation and Cancer Treatment Expansions, Terminal Disposition Phase Half-life (t1/2z) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

Measure: Dose Escalation and Cancer Treatment Expansions, Total Clearance After Intravenous Administration (CL) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

Measure: Dose Escalation and Cancer Treatment Expansions, Volume of Distribution at Steady State After Intravenous Administration (Vss) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

Description: ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR) through the study (approximately 3 years), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors and Response Evaluation Criteria in Lymphoma (RECIL) for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Overall Response Rate (ORR)

Time: From the first dose until best response is achieved (up to approximately 3 years)

Description: DOR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Duration of Response (DOR)

Time: From the time of documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study (up to approximately 3 years)

Description: DCR is defined as percentage of participants who achieve stable disease (SD) or better greater than (>) 6 weeks during the study in response-evaluable population, as determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Disease Control Rate (DCR)

Time: From the first dose until best response is achieved (up to approximately 3 years)

Description: PFS will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Progression-free Survival (PFS)

Time: From the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study (up to approximately 3 years)

Description: TTR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Time to Response (TTR)

Time: From the date of first study drug administration to the date of first documented PR or better (up to approximately 3 years)

Measure: Dose Escalation and Cancer Treatment Expansions: Percentage of Participants at Each Dose Level Demonstrating Adduct Formation in Post-dose Skin or Tumor Biopsies

Time: Up to Cycle 1 (approximately 3 weeks) (Cycle length =21 days)

Measure: Dose Escalation and Cancer Treatment Expansions: Percent Change in Small Ubiquitin-like Modifier (SUMO) 2/3 Signal With Pre and Post-dose Skin or Tumor Biopsies at Each Dose Level

Time: Up to Cycle 1 (approximately 3 weeks) (Cycle length =21 days)

Measure: COVID-19 Expansion: Number of Participants Reporting one or More TEAEs

Time: Up to 9 months

Description: Severity Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 5.0.

Measure: COVID-19 Expansion: Number of Participants Based on Severity of TEAEs

Time: Up to 9 months

Measure: COVID-19 Expansion: Number of Participants Based on Duration of TEAEs

Time: Up to 9 months

Description: CRS will be graded as per ASTCT Consensus Grading for CRS.

Measure: COVID-19 Expansion: Number of Participants who Experience CRS

Time: Up to 9 months

Description: NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Measure: COVID-19 Expansion: Change from Baseline in National Early Warning Score (NEWS)

Time: Up to 9 months

Description: Percentage of participants will be reported based on severity rating on a 6-point ordinal scale, which will include: 1 (death); 2 (hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, hospitalized); 3 (on non-invasive ventilation or high flow oxygen devices); 4 (hospitalized, requiring supplemental oxygen); 5 (hospitalized, not requiring supplemental oxygen); and 6 (not hospitalized).

Measure: COVID-19 Expansion: Percentage of Participants Reporting Each Hospitalization Severity Rating

Time: Up to 9 months

Description: Change from Baseline in SARS-CoV-2 viral Load in nasopharyngeal or oropharyngeal samples will be determined by viral response. The nasopharyngeal swab will be collected from both nostrils or from the same nostril every time.

Measure: COVID-19 Expansion: Change From Baseline in SARS-CoV-2 Viral Load in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

Measure: COVID-19 Expansion: Percentage of Participants Requiring Oxygen Supplementation; Assisted or Positive Pressure Non-invasive Ventilation; and Invasive Ventilation, on Days 3, 5, 8, 11, 15, and 30

Time: Days 3, 5, 8, 11, 15, and 30

Measure: COVID-19 Expansion: Percentage of Participants That met Intensive Care Unit (ICU) Criteria

Time: Up to 9 months

Measure: COVID-19 Expansion: Duration of Hospitalization

Time: Up to 9 months

Description: Time from the first dose of TAK-981 to viral load negativity (below level of detection).

Measure: COVID-19 Expansion: Time to Viral Ribonucleic Acid (RNA) Negativity in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

Description: Time from first dose of TAK-981 to participant's discharge or to NEWS score <=3. NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Measure: COVID-19 Expansion: Time to Discharge or to a NEWS of Less Than or Equal to (<=) 3 and Maintained for 24 Hours

Time: Up to 9 months

Measure: COVID-19 Expansion: Number of Deaths in Hospital due to any Cause in First 30 Days and in 90 Days

Time: Days 30 and 90

2 A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19

Some 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.

NCT04306705 Covid-19 SARS Cytokine Storm Cytokine Release Syndrome Tocilizumab Drug: Tocilizumab Other: Standard of care Procedure: Continuous renal replacement therapy
MeSH:Syndrome

Primary Outcomes

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 days

Secondary Outcomes

Description: Measured in days

Measure: Duration of hospitalization

Time: Up to 28 days

Description: 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 days

Description: Blood routine test

Measure: Change from baseline in white blood cell and differential count

Time: Day 1 through Day 28

Description: Oropharyngeal or anal swabs

Measure: Time to first negative in 2019 novel Corona virus RT-PCR test

Time: Up to 28 days

Description: Date and cause of death (if applicable).

Measure: All-cause mortality

Time: up to 12 weeks

Description: Serum hsCRP

Measure: Change from baseline in hsCRP

Time: Day 1 through Day 28

Description: 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 28

Description: 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)

3 Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults

This study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC + Lopinavir/Ritonavir plus interferon ß-1a versus SoC + Hydroxychloroquine. Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is the subject clinical status (on a 7-point ordinal scale) at day 15.

NCT04315948 Corona Virus Infection Drug: Remdesivir Drug: Lopinavir/ritonavir Drug: Interferon Beta-1A Drug: Hydroxychloroquine Other: Standard of care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: 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: Percentage of subjects reporting each severity rating on a 7-point ordinal scale

Time: Day 15

Secondary Outcomes

Description: Time to an improvement of one category from admission on an ordinal scale. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.

Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale

Time: Days 3, 5, 8, 11, 15 and 29

Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.

Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first.

Time: Days 3, 5, 8, 11, 15 and 29

Measure: Number of oxygenation free days in the first 28 days

Time: 29 days

Measure: Incidence of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.

Time: 29 days

Measure: Duration of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.

Time: 29 days

Measure: Ventilator free days in the first 28 days

Time: 29 days

Measure: Incidence of new mechanical ventilation use during the trial.

Time: 29 days

Description: • Duration of hospitalization (days).

Measure: Hospitalization

Time: 29 days

Description: Rate of mortality

Measure: Mortality

Time: In hospital, Day 28, Day 90

Measure: Cumulative incidence of serious adverse events (SAEs)

Time: 29 days

Measure: Cumulative incidence of Grade 3 and 4 adverse events (AEs)

Time: 29 days

Measure: Number of participants with a discontinuation or temporary suspension of study drugs (for any reason)

Time: 29 days

Measure: Changes from baseline in blood white cell count

Time: 29 days

Measure: Changes from baseline in haemoglobin

Time: 29 days

Measure: Changes from baseline in platelets

Time: 29 days

Measure: Changes from baseline in creatinine

Time: 29 days

Measure: Changes from baseline in blood electrolytes (including kaliemia)

Time: 29 days

Measure: Changes from baseline in prothrombine time

Time: 29 days

Measure: Changes from baseline in international normalized ratio (INR)

Time: 29 days

Measure: Changes from baseline in glucose

Time: 29 days

Measure: Changes from baseline in total bilirubin

Time: 29 days

Measure: Changes from baseline in alanine aminotransferase (ALT)

Time: 29 days

Measure: Changes from baseline in aspartate aminotransferase (AST)

Time: 29 days

Other Outcomes

Measure: Percent of subjects with SARS-CoV-2 detectable in nasopharyngeal sample

Time: Days 3, 5, 8, 11, 15, 29

Measure: Quantitative SARS-CoV-2 virus in nasopharyngeal sample

Time: Days 3, 5, 8, 11, 15, 29

Measure: Quantitative SARS-CoV-2 virus in blood

Time: Days 3, 5, 8 and 11

Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized

Measure: Plasma concentration of lopinavir

Time: Days 1, 3, 5, 8 and 11

Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized

Measure: Plasma concentration of hydroxychloroquine

Time: Days 1, 3, 5, 8 and 11

4 Prospective, Controlled, Randomized, Multicenter Study to Compare the Efficacy of a Chloroquine Analog (GNS561), an Anti PD-1 (Nivolumab) and an Anti-interleukine-6 Receptor (Tocilizumab) vs Standard of Care in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 (COVID-19) Infection

A prospective, controlled, randomized, multicenter study whose goal is to compare the efficacy of a chloroquine analog (GNS561), an anti PD-1 (nivolumab) and an anti-interleukine-6 receptor (tocilizumab) versus standard of care in patients with advanced or metastatic cancer who have Sars-CoV-2 infection not eligible to a resuscitation unit. According to their severity level at the time of enrolment, eligible patients will be randomized into 2 different cohorts: - COHORT 1 (mild symptoms or asymptomatic): GNS561 vs anti-PD1 vs standard of care (randomization ratio 1:1:1). - COHORT 2 (moderate/severe symptoms): GNS561 vs anti-IL6 vs standard of care (randomization ratio 1:1:1).

NCT04333914 SARS-CoV-2 (COVID-19) Infection Advanced or Metastatic Hematological or Solid Tumor Drug: Chloroquine analog (GNS651) Drug: Nivolumab Drug: Tocilizumab Other: Standard of care
MeSH:Infection Communicable Diseases Neoplasm Metastasis

Primary Outcomes

Description: 28-day survival rate, defined by the proportion of patients still alive 28 days after randomization. The 28-day survival rate will be described in each arm of each cohort.

Measure: 28-day survival rate

Time: 28 days from randomization

Secondary Outcomes

Description: Time to clinical improvement defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale (WHO-ISARIC) or live discharge from the hospital, whichever comes first.

Measure: Time to clinical improvement

Time: 28 days from randomization

Description: Clinical status will be assessed using a 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

Time: Day 7, Day 14, Day 28

Description: Mean change in clinical status from baseline will be assessed using a 7-point ordinal scale.

Measure: Mean change in clinical status from baseline to days

Time: Day 7, Day 14, Day 28

Description: Overall survival will be defined by the time from date of randomization until date of death, regardless of the cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

Measure: Overall survival

Time: 3 months (i.e. at the the time of last patient last visit)

Description: The length of stay in Intensive Care Unit (from the date of admission in the Unit to the date of discharge).

Measure: Length of stay in Intensive Care Unit

Time: 3 months (i.e. at the the time of last patient last visit)

Description: The duration of mechanical ventilation or high flow oxygen devices (from the date of intubation to the stop date of mechanical ventilation or high flow oxygen)

Measure: Duration of mechanical ventilation or high flow oxygen devices

Time: 3 months (i.e. at the the time of last patient last visit)

Description: The duration of hospitalization (from the date of hospitalization to the date of definitive discharge for live patients)

Measure: Duration of hospitalization

Time: 3 months (i.e. at the the time of last patient last visit)

Measure: Rate of throat swab negativation

Time: Day 7, Day 14, Day 28

Measure: Quantitative SARS-CoV-2 virus in throat swab and blood samples

Time: Day 7, Day 14, Day 28

Measure: Rate of secondary infection by other documented pathogens

Time: Day 7, Day 14, Day 28 (if available)

Description: Changes from baseline in neutrophils count (G/L)

Measure: Biological parameters

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Treatment-Emergent Adverse Events, Serious Adverse Events, Suspected Unexpected Serious Adverse Reactions, New Safety Issues described using the NCI-CTC AE classification v5. Number of participants with a discontinuation or temporary suspension of study drugs (for any reason).

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.

Measure: Cost-Effectiveness Analyses (CEA)

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Changes from baseline in lymphocytes count (G/L)

Measure: Biological parameters

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Changes from baseline in platelets count (G/L)

Measure: Biological parameters

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Changes from baseline in hemoglobin count (g/dL)

Measure: Biological parameters

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Changes from baseline in CRP count (mg/L)

Measure: Biological parameters

Time: 3 months (i.e. at the the time of last patient last visit)

Description: Changes from baseline in pro-inflammatory cytokine (IL6)

Measure: Biological parameters

Time: 3 months (i.e. at the the time of last patient last visit)

5 Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection

This is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens: Arm 1: Standard of care alone Arm 2: Standard of care plus hydroxychloroquine Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups: 1. Standard of care alone 2. Standard of care plus hydroxychloroquine 3. Standard of care plus azithromycin 4. Standard of care plus hydroxychloroquine plus azithromycin

NCT04335552 SARS-CoV-2 Other: Standard of care Drug: Hydroxychloroquine Drug: Azithromycin
MeSH:Infection

Primary Outcomes

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: World Health Organization (WHO) ordinal scale measured at 14 days after enrollment

Time: Day 14

Secondary Outcomes

Measure: Rates of death during the index hospitalization

Time: Index hospitalization, up to 46 days

Measure: Number of days on mechanical ventilation for patients who were on mechanical ventilation at baseline

Time: Baseline

Measure: Proportion of patients not receiving mechanical ventilation at baseline who progress to requiring mechanical ventilation during the index hospitalization

Time: Index hospitalization, up to 46 days

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: WHO ordinal scale measured at 28 days after enrollment

Time: Day 28

Measure: Hospital length of stay in days for the index hospitalization

Time: Index hospitalization, up to 46 days

Measure: Rates of all-cause study medication discontinuation

Time: Index hospitalization, up to 46 days

Measure: Rates of severe adverse events

Time: Day 14

6 Alpha-1 Adrenergic Receptor Antagonism to Prevent COVID-19 Cytokine Storm Syndrome and Acute Respiratory Distress Syndrome: A Randomized Study Comparing the Efficacy of Prazosin vs. Standard of Care for SARS-CoV-2 Infection

The purpose of this study is to assess the efficacy and safety of prazosin to prevent cytokine storm syndrome and severe complications in hospitalized patients with Coronavirus disease 2019 (COVID-19).

NCT04365257 COVID-19 Drug: Prazosin Other: Standard of care

Primary Outcomes

Description: Number of participants in each arm who expire.

Measure: Death

Time: up to day 60

Description: Number of participants in each arm who are hospitalized and requiring mechanical ventilation and/or high flow nasal cannula and/or ICU/CCU admission (or equivalent) and/or ECMO.

Measure: Hospitalized, requiring mechanical ventilation and/or high flow nasal cannula and/or ICU/CCU admission (or equivalent) and/or ECMO

Time: up to day 60

Description: Number of participants in each arm who are hospitalized and requiring supplemental oxygen, not requiring ICU/CCU level care (or interventions listed under Outcome 2).

Measure: Hospitalized, requiring supplemental oxygen, not requiring ICU/CCU level care (or interventions listed under Outcome 2)

Time: up to day 60

Description: Number of participants in each arm who develop grade 3 and 4 adverse events during the study period.

Measure: Cumulative incidence of grade 3 and 4 adverse events

Time: up to day 60

Description: Number of participants in each arm who develop serious adverse events during the study period.

Measure: Number of participants with serious adverse events

Time: up to day 60

Description: Number of participants in each arm who develop symptomatic hypotension (systolic blood pressure <90 mmHg) or hypotension requiring cessation of prazosin.

Measure: Incidence of symptomatic hypotension or hypotension requiring cessation of prazosin

Time: up to day 60

Secondary Outcomes

Description: Number of participants with laboratory abnormalities in peripheral blood (Lymphopenia, leukocytosis, anemia, thrombocytopenia, creatinine, AST/ALT, troponin I, pro-BNP, D-dimer, ferritin, interleukin (IL-6), soluble IL-2 receptor.

Measure: Number of participants with laboratory abnormalities in peripheral blood

Time: up to day 60

Description: Number of days with laboratory abnormalities in peripheral blood (Lymphopenia, leukocytosis, anemia, thrombocytopenia, creatinine, AST/ALT, troponin I, pro-BNP, D-dimer, ferritin, interleukin (IL-6), soluble IL-2 receptor.

Measure: Duration of laboratory abnormalities in peripheral blood

Time: up to day 60

Description: Number of participants with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Measure: Number of participants with laboratory abnormalities in plasma

Time: up to day 60

Description: Number of days with laboratory abnormalities in fractionated plasma catecholamines and plasma metanephrines.

Measure: Duration of laboratory abnormalities in plasma

Time: up to day 60

7 Interleukin-1 (IL-1) and Interferon Gamma (IFNg) Inhibition During COVID 19 Inflammation: Randomized, Controlled Study Assessing Efficacy and Safety of Anakinra and Ruxolitinib

During SARS-Cov2 infection with serious respiratory implication and high systemic inflammation level, intravenous ANAKINRA alone or associated with RUXOLITINIB for severe cases might reduce inappropriate systemic inflammatory response, improve breathing and decrease occurrence or duration of ARDS and associated mortality.

NCT04366232 Covid-19 Drug: Anakinra alone (stages 2b/3) Drug: Anakinra and Ruxolitinib (overcome stage 3) Other: Standard of care
MeSH:Inflammation

Primary Outcomes

Description: At least 3 parameters are met including CRP and/or Ferritin among: CRP: decrease > 50% Ferritinemia: decrease > 1/3 Serum creatinine: decrease > 1/3 AST/ALT: decrease > 50% Eosinophils > 50 /mm3 Lymphocytes > 1000 /mm3

Measure: Biological criteria

Time: 7 days from enrolment

Secondary Outcomes

Description: Number of days without mechanical ventilation

Measure: Duration of oxygen therapy (days)

Time: 28 days from enrolment

Description: Number of patients included in stage 2b

Measure: Number of intensive care units admissions

Time: 28 days from enrolment

Description: Number of days in intensive care units for patients managed in intensive care units

Measure: Number of days in intensive care units

Time: 28 days from enrolment

Description: Mortality rate

Measure: Mortality rate

Time: 28 days from enrolment

Description: Total number of days in hospital

Measure: Total number of days in hospital

Time: 28 days from enrolment

Description: Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score); Sofa score's minimum and maximum values are 0 and 24, the lowest score corresponds to a better outcome.

Measure: Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score)

Time: 28 days from enrolment

Description: Number of bacterial and/or fungal sepsis

Measure: Number of bacterial and/or fungal sepsis

Time: 28 days from enrolment

8 Phase II Clinical Trial to Explore the Efficacy of Allogeneic Mesenchymal Cells From Umbilical Cord Tissue in Patients With Severe Pulmonary Involvement by COVID-19

The disease caused by the SARS-CoV-2 virus is a viral disease that infects the lungs, producing flu-like symptoms. Elderly infected patients and/or those with co-morbidities may suffer from acute respiratory distress syndrome due to pneumonia (COVID-19 disease). Given the high transmission, this virus has spread in recent months from Wuhan (China) to the whole world, becoming a global emergency pandemic. The lack of curative treatment for this disease justifies the need to carry out clinical trials that provide quality evidence on treatment options. Given the pathophysiology of the disease, which involves an uncontrolled inflammatory response of alveolar cells, a treatment that attenuates the cytokine cascade could be key in rescuing the patient's lung tissue. Mesenchymal cells, due to their immunoregulatory potential and regenerative capacity, can be an effective treatment for patients infected with the SARS-CoV-2 virus. In the present study we propose a therapy with undifferentiated allogeneic mesenchymal cells derived from umbilical cord tissue, a treatment whose safety has already been described in other clinical trials and that shows promising results in pilot studies carried out in China.

NCT04366271 COVID Biological: Mesenchymal cells Drug: Standard of care

Primary Outcomes

Description: Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 28 days of treatment

Measure: Mortality due to lung involvement due to SARS-CoV-2 virus infection at 28 days of treatment

Time: 28 days

Secondary Outcomes

Description: Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 14 days of treatment

Measure: Mortality due to lung involvement due to SARS-CoV-2 virus infection at 14 days of treatment

Time: 14 days

Description: Percentage of patients death due to any cause at 28 days of treatment

Measure: Mortality from any cause at 28 days

Time: 28 days

Description: Number of days without mechanical respirator and without vasopressor treatment for 28 days

Measure: Days without mechanical respirator and without vasopressor treatment for 28 days

Time: 28 days

Description: Percentage of patients alive without mechanical ventilation and without vasopressors on day 28

Measure: Patients alive without mechanical ventilation and without vasopressors on day 28

Time: 28 days

Description: Percentage of patients alive and without mechanical ventilation on day 14

Measure: Patients alive and without mechanical ventilation on day 14

Time: 14 days

Description: Percentage of patients alive and without mechanical ventilation on day 28

Measure: Patients alive and without mechanical ventilation on day 28

Time: 28 days

Description: Percentage of patients alive and without vasopressors on day 28

Measure: Patients alive and without vasopressors on day 28

Time: 28 days

Description: Number of days without vasopressors for 28 days

Measure: Days without vasopressors for 28 days

Time: 28 days

Description: Percentage of patients cured at 15 days

Measure: Patients cured at 15 days

Time: 15 days

Description: Percentage of patients with each adverse event

Measure: Incidence of Treatment-Emergent Adverse Events

Time: 1 year

9 A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease

This is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. Otilimab is a human monoclonal anti-GM-CSF antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of patients with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.

NCT04376684 Severe Acute Respiratory Syndrome Biological: Otilimab Biological: Placebo Drug: Standard of care
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections

Primary Outcomes

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 28

Time: Day 28

Secondary Outcomes

Description: Number of deaths due to all causes will be assessed.

Measure: Number of deaths due to all causes at Day 60

Time: Day 60

Description: Time to death due to all causes will be assessed.

Measure: Time to number of deaths due to all causes at Day 60

Time: Day 60

Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 7

Time: Day 7

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 14

Time: Day 14

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 42

Time: Day 42

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 60

Time: Day 60

Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Time to recovery from respiratory failure

Time: Day 28

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 7

Time: Day 7

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 14

Time: Day 14

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 28

Time: Day 28

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 42

Time: Day 42

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 60

Time: Day 60

Description: Time will be recorded from dosing to last dependence on supplementary oxygen. Participants are dependent on supplementary oxygen if they are in category 4 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Time to last dependence on supplementary oxygen

Time: Day 28

Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.

Measure: Proportion of participants admitted to Intensive Care Unit (ICU)

Time: Day 28

Description: Defined as the time from dosing to when the participant is discharged from the ICU.

Measure: Time to final Intensive Care Unit (ICU) discharge

Time: Day 28

Description: Time from dosing to when a participant is discharged from the hospital.

Measure: Time to final hospital discharge

Time: Day 28

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence, that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.

Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)

Time: Up to Day 60

10 Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19

This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.

NCT04380376 COVID-19 Viral Pneumonia Drug: Melphalan Other: Standard of care
MeSH:Pneumonia, Viral Pneumonia Respiratory Aspiration
HPO:Pneumonia

Primary Outcomes

Description: The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) Death Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT Hospitalized with intubation and mechanical ventilation Hospitalized on non-invasive ventilation or high flow oxygen. Hospitalized on a mask or nasal prongs. Hospitalized no oxygen therapy. Ambulatory, with limitation of activities. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.

Measure: The changes of COVID Ordinal Outcomes Scale

Time: baseline vs Day 14, day 28

Description: Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.

Measure: Percentage of the patients with Clinical Recovery

Time: baseline vs day 7, day 14, day 28

Description: The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.

Measure: The changes of the Borg's scale

Time: Baseline vs day 7, day 14, day 28

Secondary Outcomes

Description: Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.

Measure: CRP level

Time: baseline, day 7, Day 14, Day 28

Description: Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.

Measure: Lymphocyte count

Time: baseline, day 7, Day 14, Day 28

Description: Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.

Measure: D-dimer

Time: baseline, day 7, Day 14, Day 28

Description: Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.

Measure: IL-6

Time: baseline, day 7, Day 14, Day 28

Description: Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.

Measure: Percentage of patients without artificial lung ventilation

Time: baseline, day 7, Day 14, Day 28

11 mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms (TACTIC-E)

TACTIC-E is a randomised, parallel arm, open-label platform trial for investigating potential treatments 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 COVID-19 appears to be due to a later, exaggerated, host immune response (Gralinski and Baric 2015). 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. This study will assess the efficacy of a novel immunomodulatory agent and a novel combination of approved agents which may protect the patient against end-organ damage and modulate the pulmonary vascular response. This study will compare the novel therapeutic agent EDP1815 and a novel combination of the approved agents dapagliflozin and ambrisentan against Standard of Care. Reference: Gralinski and Baric 2015. Molecular pathology of emerging coronavirus infections. J Pathol 2015: 235: 185-195; DOI: 10.1002/path.4454

NCT04393246 COVID-19 Drug: EDP1815 Drug: Dapagliflozin Drug: Ambrisentan 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/vassopressors) 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 14

Secondary Outcomes

Description: Change in serum/plasma levels of IL-6, Ferritin, CRP, D-Dimer, neutrophil to lymphocyte ratio, and LDH compared to baseline

Measure: Change in biomarkers known to be associated with progression of COVID-19 compared to baseline

Time: 14 days

Description: For patients receiving EDP1815: change in serum/plasma levels of IL-8, TNF, IL-1β, IL-10, IL-17, IL-13 compared to baseline For patients receiving Dapagliflozin+Ambrisentan: change in serum/plasma levels of ET-1, TNF compared to baseline

Measure: Change in therapy-specific markers of pharmacodynamic response in patients receiving EDP1815 or Dapagliflozin+Ambrisentan compared to baseline

Time: 14 days

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 days

Description: Number of days taken for occurrence of each of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes/vassopressors) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73m^2), haemofiltration or dialysis

Measure: Time to each of the individual endpoints of the composite primary outcome measure

Time: 14 days

Description: The proportion of patients in each treatment arm that experience adverse events of special interest, defined as: Diabetic ketoacidosis in patients on Ambrisentan & Dapagliflozin, New peripheral oedema in patients on Ambrisentan & Dapagliflozin arm

Measure: Proportion of patients with adverse events of special interest in each treatment arm

Time: 14 days

Description: The time taken to achieve blood oxygen saturation levels above 94% in patients on room air, measured in hours/days (chronically hypoxic individuals will be excluded from this analysis)

Measure: Time to Sp02 >94% on room air

Time: 14 days

Description: 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 days

Description: The duration of oxygen therapy given to a patient, measured in days

Measure: Duration of oxygen therapy

Time: 14 days

Description: The duration of hospitalisation of a patient, measured in days

Measure: Duration of hospitalisation

Time: 14 days

Description: The number of deaths recorded at 28 days irrespective of the cause

Measure: All-cause mortality at day 28

Time: 28 days

Description: 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 days


Related HPO nodes (Using clinical trials)


HP:0004377: Hematological neoplasm
Genes 347
KRAS PDGFRA IL2RG SRP54 IL2RG NPM1 TET2 FLT3 ITK SMPD1 PRKCD GATA1 KIT RPL11 RUNX1 CALR ATRX TNFRSF1B DCLRE1C SAMD9L EVC2 CD70 BRAF TSR2 SPINK1 RNF43 FASLG ATM CASP10 NRAS BCL10 BUB1 SH2B3 RPS29 CEBPA TP53 CHD7 TINF2 MYSM1 ASXL1 UBE2T CR2 CALR SETBP1 RNASEH2B KLHDC8B MALT1 TINF2 RAF1 STS TERT BCR SRP54 SRP54 TNFSF12 MLH1 RPL18 ELANE DNASE1L3 CBL MAGT1 TYROBP ASXL1 FOXP1 IL7R TCF4 FANCE DNAJC21 RPL15 FANCL KIF11 TP53 COL14A1 MPL HSPA9 IFIH1 SCN11A RPS10 JAK2 DNMT3A CTRC BCL2 LIG4 GINS1 TERC FANCG SF3B1 ELANE NBN NHP2 NUP214 MYC ETV6 CD81 TNFSF12 RNASEH2A BRIP1 BCR BUB1B RPL5 NBN FANCF IGH DNAJC21 TNFRSF1B CCND1 RMRP XRCC2 MSH6 FAS IGH NFKB2 RECQL4 CD28 BUB1B CTLA4 ARHGAP26 RPL35 CBL RAD54L POLE PALB2 GNB1 MDM2 CBFB ADAR ADA RPS17 PARN RPS14 BCR POT1 ABL1 TNFRSF13C FANCE TNFRSF13B ABL1 ICOS TET2 CD27 NFKB1 CALR LIG4 SH3GL1 CD28 PNP F13B USB1 RPL26 RPL31 PTPN11 TP63 RAD51 MPL TET2 PTPN11 ADA NUTM1 STAT3 RAG2 PIGL PRSS1 TET2 NRAS PRF1 FANCA GFI1 ATRX FANCD2 SCN9A TET2 EVC TNFRSF13C BLM RB1 FANCM SH2B3 RTEL1 HAX1 FANCC RAD54B BIRC3 GFI1 RPS15A RPS14 GFI1B RPS19 RPL35A MSH2 TCF4 RFWD3 NF1 TRIP13 PIGA GATA2 ATM SAMD9L DDX41 IGH FANCD2 RASGRP1 CASP10 MLLT10 ADA2 LIG4 MPL RUNX1 BRCA2 CD19 ERCC4 TP53 RMRP RAD51C NUP214 JAK2 SBDS SH2D1A WAS SMARCD2 THPO ZAP70 TREM2 RPS24 KIT JAK2 BLM BRCA1 RNASEH2C MYD88 RFWD3 SAMD9 SLX4 TNFRSF13B SH2B3 GLI1 CHEK2 NPM1 TET2 DKC1 GATA2 MS4A1 ICOS CALR RPS19 DKC1 LIG4 SRSF2 CR2 GATA2 RAG1 PRKCD BCL6 TREX1 RPS27 RPS26 FANCG GBA FANCI LYST SAMHD1 TET2 GATA2 LIG4 PICALM DNAJC21 NTHL1 JAK2 BUB3 TCIRG1 RPS28 FANCA MPL DYNC2LI1 DNMT3A AAGAB FANCC RARA PIK3CA TERC PGM3 MAD2L2 MYD88 MLH1 FANCB MSH6 KRAS TERT RPS7 RUNX1 MCM4 BCL10 XIAP LPP BRCA2 CD19 BRD4 PIK3R1 PTEN NAGS NBEAL2 F13A1 CTC1 SBDS HLA-DRB1 WRAP53 TAL1 EFL1 NOP10 JAK2 FLT3 CEP57 KRAS APC PMS2 WIPF1 JAK2 TERC CTLA4 GATA1 NSUN2 BCL10 XRCC4 NBN SF3B1 FAS PDGFRB RHOH MSH2 RECQL4 TAL2 PIGL RPL27 EP300 CHIC2 CCND1 TET2 GATA2 NUMA1 TERT MPL THPO CREBBP SCN10A CDKN2A ERBB3 SRP72 TERT
Protein Mutations 0
SNP 0
HP:0002664: Neoplasm
Genes 1489
WHCR ATP7A PHOX2B KRT17 IL2RG HMGA2 PORCN KRAS TET2 IDH2 FLT3 ERCC4 AR BRCA1 BRCA2 GATA1 TCF4 TCTN3 GPR101 SMAD7 KRT6B PIK3CA KCNJ10 MAP2K2 REST TTC37 MC2R TRPS1 SIX6 ALX4 PIK3CA BRAF TP53 STK11 TSR2 EXT2 EDN1 RNF43 TRNL1 ATM SDHC EXT1 BCL10 BAP1 NF1 OCRL TP53 CHD7 TINF2 ERCC6 NF1 MAFA PMS2 ASXL1 PHOX2B CTNNB1 CR2 RET TCTN3 C11ORF95 PTPN3 PIEZO2 ABCB11 SETBP1 PDCD10 LRP5 LMOD1 MALT1 ASXL1 LZTR1 TINF2 RAD51C RECQL4 MAP2K1 FOXO1 PTCH2 RPS20 FLI1 BMPR1A SMARCAD1 BMPR1A MAP3K8 DNASE1L3 SUFU TP53 FOXP1 PTCH1 PDGFRB ND1 PIK3CA ZSWIM6 SETD2 INS NRAS HBB MEN1 AIP CLCNKB RPS10 HFE COX2 TSC2 DHH CTRC MEN1 EYA1 BRCA1 GINS1 MSH3 GLI2 TRNS1 HABP2 SSX1 SUFU PRKN CD81 TNFSF12 MYH11 KIT VEGFC WWOX H19 SDHD FGF3 TNFRSF1B RMRP XRCC2 HRAS MTM1 EPHB2 PLCD1 NBN CDKN1B TUBB RECQL4 EDNRB VHL ACAN MSH6 CDKN2B DCC TJP2 HRAS CDKN2A VHL REST NKX2-1 ANTXR1 RPL35 DNM2 FGFR3 SNAI2 NLRP1 ACTG2 GNB1 EWSR1 CBFB NSD1 FLCN ERBB2 MLH1 H19 EIF2AK4 RPL10 TMEM107 TRNK RAD54L RAD51C INPP5E NFKB1 CDKN1A KDM6B F13B SLC26A2 TRNS1 RPL26 CYLD H19 PTEN PTPN11 DCLRE1C MPL FLCN NEK1 MITF MSH3 NUTM1 IL7 STAT3 TRNS2 TG ERCC3 MNX1 NRAS MLH3 TSC1 GLI3 CDK4 SDHC NF1 BRCA2 CIB1 ATRX BRCA2 ADAMTS3 ZFPM2 COL2A1 TET2 ZIC2 SLCO2A1 BLM GJA1 MAP3K1 PIK3CA SDHA RTEL1 CDK4 KCNH1 SH2B3 APC ESCO2 FANCC TERT USP9X APC RAD54B NF2 SDHB RPS14 PPP2R1B RPS19 RPL35A MSH2 WRAP53 RASA1 LMNA ACVRL1 POLH SDHB DIS3L2 PIGA GNPTAB CXCR4 MSH2 SLC25A13 BMP2 NNT PSENEN FOXI1 APC IL1RN MITF ACD PTEN MPL RUNX1 ERCC3 ERCC4 DLEC1 CHEK2 BRCA2 JAK2 SBDS BRCA1 SDHD SEMA3D MSH6 HFE TREM2 APC CCDC22 MINPP1 DISP1 FAM20C MAP2K1 ALK BRCA1 STIM1 SLC25A13 RFWD3 HRAS GLI1 TET2 DVL3 COL7A1 HMBS TFAP2A ICOS CALR PTEN UROD DKC1 FDPS LIG4 TXNRD2 SRSF2 ND5 SDHD CHEK2 NRAS BCL6 GPC3 XPC MEN1 ERCC2 AXIN2 MYC RAD51 GBA KIF1B SDHB EXT2 EXT2 NTHL1 SRY RPGRIP1L MPL MTOR CASP8 RB1CC1 IGF2 FANCC ERCC4 WRN PGM3 VHL ING1 PLAG1 WT1 MYLK KLLN PIK3CA G6PC RPS7 MCM4 ANTXR1 POLH BRCA2 DLL1 OGG1 WRN F13A1 SBDS EFL1 TAF15 GLI3 GPC3 KRAS CDKN2B MAPK1 DIS3L2 GPR101 NRTN DKC1 KLLN NSUN2 MAP3K1 ERBB2 PHKG2 SRGAP1 CYLD NBN ALK MAX WT1 ACTB PALB2 TBX18 FIBP CASP10 DVL1 TYR MSH2 RECQL4 PIGL EDN3 WT1 ATP7B RPL27 RET USP8 FGFR2 PDGFRL H19 CCND1 ATM AXIN2 COL7A1 AKT1 TERT MUTYH HOXD13 DICER1 THPO GDF5 CEL SDHB EXT2 SRP72 TERT TRNF TP53 LIN28B APC NPM1 FGFR3 PTEN SMPD1 SLC22A18 SDHC PRDM16 KIT STK11 RPL11 LETM1 CALR SDHC RB1 PIK3CA PLCB4 COL4A5 CASP8 SKI H19 COL1A1 CC2D2A CASP10 GCGR GLI3 PIK3CA RPS29 RSPO1 PTEN MYSM1 BAP1 SRY UBE2T BRCA1 USP8 COL7A1 RNASEH2B KIF1B MN1 RELA SMAD4 VHL SH3KBP1 BCR CD79B SRP54 SRP54 SSX2 CHRNG RPL18 NF1 WWOX RERE LZTS1 WT1 MSH3 TYROBP ASCL1 IKBKG ABCC6 FAH KIT GDNF FANCE TERT BIN1 FANCL KIF11 SDHB WDPCP SLC6A17 TP53 HNF1A KEAP1 POLE HSPA9 SMO PTCH2 PTCH1 PMS1 ELMO2 BCL2 NSD2 EXT1 SRD5A3 STAT6 MVD TERC SF3B1 MNX1 FGFR1 CYSLTR2 POU2AF1 SMARCB1 NOD2 GJB2 SDHC FLT4 KRT9 CDH1 IRF1 SEC23B MYCN MGMT RPL10 RPL5 KIF7 TCF3 KRAS MUTYH TMEM127 KRAS IGH CTSC GNAS CD28 WWOX HNF1A BUB1B MC1R WNT10A CBL WT1 BRAF ADAR GAS1 GTF2E2 SMARCB1 RPS17 PARN TMEM127 BRIP1 SHH SRC GNAI3 STAR GDNF SLC22A18 FOXH1 SNAI2 GPC4 TNFRSF13C KARS1 TBC1D24 BMPR1A TET2 CD27 CASP8 DHCR7 KDSR HNF1A SH3GL1 PNP USB1 TSC2 TRIP13 TMEM67 EDN3 PMS1 PTPN11 GNA11 CREB1 ADA RAG2 PRSS1 KCNQ1 GPR101 PRF1 MTAP FANCA MSH6 TRNQ BRCA2 KRT1 RNASEL POU6F2 ACD SCN9A APC NSD2 INTU BRAF POU6F2 BRCA2 RB1 GTF2H5 PIK3CA FANCM TARS1 BRAF CASR RET VHL GPR143 TRNP GCM2 TMEM231 CPLANE1 RPS15A SOX9 GFI1B EPCAM MEN1 TERT KRAS SDHAF2 NF1 TRIP13 GATA2 SLC26A4 APC MPLKIP SAMD9L IL6 GNAS IGH AKT1 FANCD2 ESR1 SDHA APC MYF6 RASGRP1 SMAD4 MLLT10 LIG4 CPLANE1 BRCA2 MC1R MRE11 DLST SUFU LMO1 SDHB ABCA5 RMRP SDHC NUP214 AKT1 SMARCD2 DLC1 C1S TRNW THPO CHEK2 KIT SLC37A4 BCHE KCNJ11 ARID1B APC2 SAMD9 TMC6 SLX4 TNFRSF13B FGFR1 TRNH RAD21 KCNN3 DKC1 VANGL1 AXIN2 TCOF1 RPS19 SLC26A2 GPR35 CR2 TFAP2A KRAS FGFR3 PRKCD JAK2 EGFR AIP CTNNB1 KCNJ10 FANCI LYST TET2 SLC25A11 TP53 TCTN3 MUTYH ANTXR2 SEMA3C MMP1 AKT1 PDX1 JAK2 TCIRG1 PTCH1 MUC5B EXT1 DNMT3A BMPR1A SERPINA1 FAN1 CDC73 PTCH2 PIK3CA H19 FERMT1 GPC3 RET RET APC PALLD LPP BRD4 GNAS BMPR1B MAPRE2 DICER1 CTC1 TAL1 DICER1 STK11 HRAS GATA1 BCL10 KCNE3 XRCC4 HNF4A BDNF KLF11 SF3B1 MLH3 GNAQ TRPV3 IGLL1 PAX7 CRKL GDNF GATA2 ARL6IP6 ENG PTCH1 NEK9 TSC1 RNF139 ERCC3 PDGFRA IL2RG CTHRC1 WT1 BAP1 ATP7A SRP54 ABCC8 ESCO2 GPC4 OFD1 TNFSF15 APPL1 RNF6 CTSA TNFRSF1B TP53 PHOX2B DCLRE1C DDB2 BCL10 BCR KRT14 ALX3 EVC2 CD70 SMARCB1 AHCY SDHAF2 RAD51D SPINK1 SDHD ATM GABRD WT1 FASLG CTBP1 NOTCH1 NF2 DPM1 ERCC6 STS PHOX2B BUB1 FLT4 L2HGDH LAMC2 NTHL1 STAG3 ENG SDHD CTNNB1 DAXX NRAS MST1 MSTO1 SLC26A4 RAF1 STS FGFR3 EXOC6B VAMP7 NELFA HRAS ANTXR2 LEMD3 TNFSF12 GPC4 MLH1 SMAD4 RAD50 SUFU TRIP13 REST GNAS CBL RHBDF2 ASXL1 SMAD4 TCF4 ERCC6 WT1 BRAF APC TRIM28 TERT DNAJC21 RPL15 PAX3 SETBP1 CDH1 GNAS SMARCB1 AKT1 ASCL1 KRAS NAB2 ERCC5 RECQL4 KRAS DNMT3A EDN3 POLD1 FAM149B1 CDKN1C KRAS TP53 SMARCE1 PTEN PALB2 SEMA4A TEK NBN NHP2 GPC3 ETV6 FGF8 COL11A2 SMAD4 RNASEH2A NRAS MC1R TDGF1 FGFRL1 FGFR1 CTNNB1 IGH DNAJC21 CCND1 RET DIS3L2 DHCR24 CARD14 BRCA2 SQSTM1 NFKB2 TRNQ NDP SFTPA2 PAX4 COL7A1 TP53 RSPRY1 IFNG HMMR PALB2 FAT4 MBTPS2 MDM2 KRAS GNAS C2CD3 POT1 ABL1 WNT5A FANCE ABL1 ICOS SDHD RAD21 NSD1 SOS1 IL12A LIG4 PIK3CA TBXT RAD51 EWSR1 FZD2 FLNA BRCA2 NRAS TWIST1 TET2 TSC1 INHBA CAT CTNNB1 PIGL IRF1 PTCH2 TRNH MLH1 GFI1 CDC73 RET FANCD2 EVC NF2 TNPO3 SOX2 DYNC2H1 HRAS NEK1 CCND1 KRT10 AKT1 KIT PALB2 VHL CYLD IL1B GJC2 MLH1 SDHC FGFR2 CYP2A6 FOXE1 ARMC5 ERCC2 SLC25A11 LAMA3 FLCN BRCA1 BIRC3 MVK TOP2A PDGFB TCF4 RFWD3 ATP6V1B2 GDNF GATA4 CTNNB1 CDKN1B C2CD3 BRCA2 FUZ STK11 AKT1 FGFR2 SHOX TGFBR1 BTK LEMD3 FIBP SF3B1 SUFU PRLR NR5A1 FN1 ERBB2 CD19 RNR1 PTPN11 KIT RAD51 WAS PTEN TGFBR2 RPS24 CYLD RNF113A MYO1H ALX3 JAK2 BLM CTNNB1 CDKN2A PARN SH2B3 POLD1 CHEK2 COX1 KRT1 EXT1 BRAF PRCC MSH2 GATA2 REST NRAS RB1 TINF2 BMPR1A NR4A3 AGGF1 SIX3 RAG1 ND4 COL2A1 CDKN2A SDHD TREX1 WNT10A SEC23B XPA MET TP53 CDKN1B RPS27 PCNA HMBS RPS26 KIT FGFR2 TRIM37 HPGD ERCC5 PAX6 SLX4 PICALM PSAP FCN3 BMPR1A USF3 XPC DNAJC21 KRT16 BUB3 H19-ICR GPC6 STAC3 RPS28 FANCA RNF43 AP2S1 PDGFB DYNC2LI1 CYP11B1 ABCA5 PTCH1 TERF2IP KRAS DYNC2LI1 CDH1 CDC73 TERC SPRED1 PDGFB TRNF MTMR14 MAD2L2 FOXI1 ERCC2 GJB4 KAT6B MSH6 FASLG KRAS SEC23A RUNX1 CD19 WASHC5 KIT HLA-DRB1 WRAP53 FLT3 CEP57 KDR TREX1 TMEM216 PDGFRA ERCC3 KIT NOTCH3 WIPF1 TERC CTLA4 NQO2 CDKN2A RSPO1 STK4 PTPN11 GJB2 KRAS MET SPINK1 PDGFRB RHOH BUB1 ND6 CDKN2C TFE3 EP300 CHIC2 HNF1B NUMA1 BRCA1 SRY FLCN MLH3 SCN10A GNPTAB KRAS NODAL TGFBR2 PPM1D DOCK8 EPAS1 PHOX2B OCA2 KCNQ1OT1 CYP2D6 ITK DICER1 PRKCD ASPSCR1 SUFU IDH1 RUNX1 ATRX FOXC2 MFN2 SAMD9L SCN4A KIF1B DHH POLE VHL POLR1D KCNAB2 BRAF SLC12A3 CARMIL2 ENPP1 NRAS LRRC8A KIT SH2B3 MST1R CEBPA NRAS MRAP TP53 ND5 FH LAMB3 CALR SLC37A4 PERP KLHDC8B FH SFTPC TGIF1 CHEK2 SLC17A9 SLC22A18 TERT CDH23 MDH2 KRT17 PTEN FGFR3 RB1 YY1 ELANE EP300 SPRTN GJB3 XPA IDH2 MAGT1 ATR GNA14 OFD1 IL7R GREM1 ESCO2 HRAS PRKAR1A MMP1 TP53 KRT17 COL14A1 RHBDF2 MPL OFD1 RYR1 IFIH1 SCN11A IDH1 JAK2 WT1 TP53 ARSA LIG4 CCBE1 FANCG KCNH1 ELANE COL18A1 HACE1 NUP214 MYC CD79A AR CDH1 BRIP1 WT1 BCR BUB1B ERCC3 KRIT1 NBN IGF2 FANCF PDGFRA BLNK PCGF2 MSH6 MEN1 FAS BRIP1 PTH1R SIX1 RNF6 BRAF DHCR7 BMPER BUB1B TP53 RET CTLA4 HABP2 ARHGAP26 DLST GCK ERCC2 RAD54L POLE HSPG2 GNA11 ADA SMAD4 BCL10 RB1 STAT1 TAF1 RPS14 BCR IL12RB1 IRF5 TMC8 TNFRSF13B CYP26C1 CALR POT1 MINPP1 POLR1C CD28 ATP7A HNF1B ERCC2 ACVR1 RPL31 VANGL1 TP63 ERCC4 SLC45A2 OFD1 LMX1B PIK3CA ASCC1 TET2 IGF2R BARD1 TUBB IGF2 BTK MSTO1 CIB1 PHB CDKN2A TNFRSF10B KIAA0753 TBX2 FOXE1 EPCAM TNFRSF13C SLC26A2 ATRX MGAT2 SKIV2L CXCR4 PIK3R1 RTEL1 TSC1 HAX1 SDHB PRKAR1A DDB2 GFI1 CDH23 XRCC3 PMVK TP53 PIK3CA GJB2 NF2 KLF6 AR ZSWIM6 SDHB CDC73 PIK3CA CCND1 GJB6 ATM SOS1 NOTCH3 DDX41 TSC2 FLT4 FGFR3 RASA1 GDF2 F5 PMS2 PTEN HBB TSC2 CASP10 ADA2 AIP WT1 LETM1 PNP COMP TRIM28 TP53 PALB2 RAD51C CCL2 CDC73 SH2D1A COX3 ZAP70 PIK3CA CYP11B2 PDGFRB PTPN11 PHOX2B FH KIT HNF4A RNASEH2C MYD88 PDE6D JAG1 TYR SEC23A FH NPM1 PHKA2 DICER1 PIK3CA HFE GNAQ DMRT3 MS4A1 MYH8 VANGL2 SHOX PUF60 GATA2 BAP1 B3GALT6 TRNS2 HRAS HDAC4 FANCG SAMHD1 GATA2 LIG4 AXIN1 TNFRSF4 OPCML PRKN FGFR2 ECM1 TGFBR2 LMNA WDPCP KCNQ1OT1 BLK GCM2 ALX1 NRAS KIT AAGAB FAH MAX RARA NEUROD1 TGFBR2 MYD88 PHF21A IDH1 MLH1 FANCB CPLX1 SMARCA4 EXTL3 AIP TERT BCL10 XIAP IGF2 SASH1 PIK3R1 PTEN NAGS TMC6 NBEAL2 NOP10 JAK2 SDHB MSH2 ECE1 BARD1 APC PMS2 CCM2 JAK2 MMEL1 RET SDHA SDHD IGHM CACNA1S FAS NR0B1 POT1 SPIB TAL2 NF2 CDON WT1 TET2 PTPRJ CD96 TRNL1 DOCK8 DCC MPL GNAQ CREBBP CDKN2A TRNK MSR1 KRT5 PRKAR1A ERBB3