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Coronavirus Infections (808) Severe Acute Respiratory Syndrome (560) Infection (466) Pneumonia (365) Communicable Diseases (197) Respiratory Distress Syndrome, Adult (178) Acute Lung Injury (143) Respiratory Distress Syndrome, Newborn (143) (130) Syndrome (105) Virus Diseases (87) Pneumonia, Viral (82) Depression (65) Critical Illness (62) Anxiety Disorders (38) Respiratory Tract Infections (36) Cardiovascular Diseases (35) Emergencies (35) Stress, Psychological (31) Lung Injury (30) Neoplasms (30) Inflammation (29) Stress Disorders, Post-Traumatic (29) Wounds and Injuries (29) Hypoxia (28) Thrombosis (28) Diabetes Mellitus (26) Disease (25) Respiratory Tract Diseases (25) Stress Disorders, Traumatic (25) Depressive Disorder (24) Acute Kidney Injury (22) Disease Progression (22) Lung Diseases (22) Mental Disorders (21) Burnout, Psychological (19) Olfaction Disorders (19) Respiration Disorders (19) Thromboembolism (19) Hypertension (18) Embolism (16) Arthritis (15) Blood Coagulation 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D055370: Lung Injury

Developed by Shray Alag, The Harker School
Sections: Correlations, Clinical Trials, and HPO

Correlations computed by analyzing all clinical trials.

Navigate: Clinical Trials and HPO


Correlated Drug Terms (92)


Name (Synonyms) Correlation
drug203 Ampion Wiki 0.26
drug3253 TD-0903 Wiki 0.26
drug1737 Knowledge, Attitude, Practice, Awareness, Preference Wiki 0.18
Name (Synonyms) Correlation
drug399 Baseline message Wiki 0.18
drug325 Aviptadil by intravenous infusion + standard of care Wiki 0.18
drug287 Assessing impact of COVID19 Wiki 0.18
drug2756 Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) Wiki 0.18
drug2801 Respiratory Exercise Training Wiki 0.18
drug225 Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki 0.18
drug3860 mMRC (Modified Medical Research Council) Dyspnea Scale Wiki 0.18
drug2413 Personal freedom message Wiki 0.18
drug118 AVIGAN Wiki 0.18
drug2219 Not bravery message Wiki 0.18
drug858 Control message Wiki 0.18
drug15 0.9% Sodium-chloride Wiki 0.18
drug2125 Nebulized administration of RLF-100 or Placebo Wiki 0.18
drug2790 Remote Ischemic Conditioning Wiki 0.18
drug156 Additional and minimal collection of products of the human body carried out during a sample for standard of care Wiki 0.18
drug251 Antioxidation Therapy Wiki 0.18
drug2992 Self-interest message Wiki 0.18
drug1350 Glucose tablets Wiki 0.18
drug1895 MSCT Wiki 0.18
drug2743 Rapamycin Wiki 0.18
drug209 Anakinra Prefilled Syringe Wiki 0.18
drug1122 Economic freedom message Wiki 0.18
drug3065 Six-minute walk test (6MWT) Wiki 0.18
drug1046 Dociparastat sodium Wiki 0.18
drug2119 Nebulised heparin Wiki 0.18
drug3265 Tacrolimus Wiki 0.18
drug2546 Plethysmography & DLCO Wiki 0.18
drug1373 Guilt message Wiki 0.18
drug1147 Embarrassment message Wiki 0.18
drug2757 Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) plus Aerosolized 13 cis retinoic acid Wiki 0.18
drug3768 eculizumab Wiki 0.18
drug433 Biological collection (patients co infected HIV Sras-CoV-2) Wiki 0.18
drug216 Anger message Wiki 0.18
drug3107 St. George's Respiratory Questionnaire (SGRQ) Wiki 0.18
drug340 Azithromycin 500Mg Oral Tablet Wiki 0.18
drug816 Community interest message Wiki 0.18
drug2668 Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki 0.18
drug3384 Tocilizumab Prefilled Syringe Wiki 0.18
drug541 CAStem Wiki 0.18
drug3437 Trust in science message Wiki 0.18
drug1861 Lucinactant Wiki 0.18
drug2850 Ruxolitinib administration Wiki 0.18
drug126 AZD1656 Wiki 0.18
drug1121 Economic benefit message Wiki 0.18
drug136 Acalabrutinib Wiki 0.18
drug237 Anti-SARS-CoV2 serological controls and serum neutralization Wiki 0.18
drug3508 V/Q SPECT-CT Wiki 0.18
drug183 Airwave Oscillometry Wiki 0.18
drug2210 Normal Saline Infusion + standard of care Wiki 0.18
drug3515 VIB7734 Wiki 0.18
drug317 Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki 0.18
drug2739 Ramelteon 8mg Wiki 0.18
drug3077 Sodium Nitrite Wiki 0.18
drug2377 Patient Education Wiki 0.18
drug1863 Lung CT scan analysis in COVID-19 patients Wiki 0.18
drug1348 Gimsilumab Wiki 0.18
drug546 CERC-002 Wiki 0.18
drug2651 Pulmonary and Motor Rehabilitation Wiki 0.18
drug3170 Standard-of-care treatment Wiki 0.18
drug1862 Lung CT Wiki 0.18
drug1741 L-ascorbic acid Wiki 0.13
drug2722 RLF-100 (aviptadil) Wiki 0.13
drug166 Aerobic Exercise Training Wiki 0.13
drug143 Acebilustat Wiki 0.13
drug305 Atorvastatin Wiki 0.13
drug3054 Simvastatin Wiki 0.13
drug3104 Spirometry Wiki 0.13
drug1486 Hydroxychloroquine 200 Mg Oral Tablet Wiki 0.13
drug2472 Placebo Comparator Wiki 0.13
drug3138 Standard of Care Wiki 0.11
drug236 Anti-SARS-CoV2 Serology Wiki 0.11
drug2751 Ravulizumab Wiki 0.11
drug1566 Ibrutinib Wiki 0.11
drug1640 Interferon beta-1a Wiki 0.11
drug130 Abatacept Wiki 0.11
drug2448 Placebo Wiki 0.10
drug2208 Normal Saline Wiki 0.09
drug1404 Heparin Wiki 0.09
drug418 Best Supportive Care Wiki 0.09
drug2723 RLS-0071 Wiki 0.09
drug281 Aspirin Wiki 0.08
drug671 Camostat Wiki 0.08
drug2304 Oseltamivir Wiki 0.07
drug1824 Losartan Wiki 0.06
drug1995 Methylprednisolone Wiki 0.05
drug2685 Questionnaire Wiki 0.03
drug2782 Remdesivir Wiki 0.03
drug333 Azithromycin Wiki 0.03
drug1472 Hydroxychloroquine Wiki 0.02

Correlated MeSH Terms (16)


Name (Synonyms) Correlation
D055371 Acute Lung Injury NIH 0.34
D012128 Respiratory Distress Syndrome, Adult NIH 0.31
D014947 Wounds and Injuries NIH 0.24
Name (Synonyms) Correlation
D012127 Respiratory Distress Syndrome, Newborn NIH 0.18
D063806 Myalgia NIH 0.18
D004417 Dyspnea NIH 0.12
D013577 Syndrome NIH 0.07
D011024 Pneumonia, Viral NIH 0.06
D011014 Pneumonia NIH 0.06
D007251 Influenza, Human NIH 0.06
D007249 Inflammation NIH 0.03
D018352 Coronavirus Infections NIH 0.03
D045169 Severe Acute Respiratory Syndrome NIH 0.03
D016638 Critical Illness NIH 0.02
D014777 Virus Diseases NIH 0.02
D007239 Infection NIH 0.02

Correlated HPO Terms (3)


Name (Synonyms) Correlation
HP:0003326 Myalgia HPO 0.18
HP:0002098 Respiratory distress HPO 0.12
HP:0002090 Pneumonia HPO 0.06

Clinical Trials

Navigate: Correlations   HPO

There are 30 clinical trials


1 RLF-100 for the Treatment of Critical COVID-19 With Respiratory Failure

Novel Corona Virus (SARS-CoV-2) is known to cause Respiratory Failure, which is the hallmark of Acute COVID-19, as defined by the new NIH/FDA classification. Approximately 50% of those who develop Critical COVID-19 die, despite intensive care and mechanical ventilation. Patients with Critical COVID-19 and respiratory failure, currently treated with high flow nasal oxygen, non-invasive ventilation or mechanical ventilation will be treated with Aviptadil, a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.

NCT04311697
Conditions
  1. Critical COVID-19 With Respiratory Failure
  2. Acute Respiratory Distress Syndrome (ARDS)
  3. Corona Virus Infection
  4. Acute Lung Injury
Interventions
  1. Drug: Aviptadil by intravenous infusion + standard of care
  2. Drug: Normal Saline Infusion + standard of care
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury

Primary Outcomes

Description: Cumulative distribution of the time to respiratory failure resolution with concurrent survival through day 28

Measure: Resolution of Respiratory Failure

Time: Day 0 through day 28

Secondary Outcomes

Description: Achievement of score 6-8 on NIAID Ordinal Scale through day 28

Measure: Improvement on NIAID Scale (key secondary measure)

Time: Day 0 through day 28

Description: Survival probability on Kaplan Meier lifetable through day 28 and day 60

Measure: Survival through day 28 and day 60

Time: Day 0 through day 28

Description: Time to discharge from Intensive Care Unit

Measure: Time to ICU discharge

Time: Day 0 through day 28

Description: Time on mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen

Measure: Time on ventilation

Time: Day 0 through day 28

Description: Time to extubation (for those initially on mechanical ventilation)

Measure: Time to extubation

Time: Day 0 through day 28

Description: Time to discharge alive

Measure: Time to discharge alive

Time: Day 0 through day 28 and day 60

Description: Days free of multisystem organ failure

Measure: Multi-organ failure free days

Time: Day 0 through day 28

Other Outcomes

Description: PaO2:FiO2 ratio

Measure: Respiratory Distress while on mechanical ventilation

Time: Day 0 through day 28

Description: Oxygenation index

Measure: Oxygenation index

Time: Day 0 through day 28

Description: Improvement in chest x-ray by RALES score

Measure: Improvement in chest x-ray

Time: Day 0 through day 28

Description: Improvement in IL-6, TNF alpha, and other inflammatory markers

Measure: Improvement in inflammatory markers

Time: Day 0 through day 28
2 Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)

A phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.

NCT04331613
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Virus; Pneumonia
  4. Acute Lung Injury
Interventions
  1. Biological: CAStem
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Description: Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment

Measure: Adverse reaction (AE) and severe adverse reaction (SAE)

Time: Within 28 days after treatment

Description: Evaluation by chest CT

Measure: Changes of lung imaging examinations

Time: Within 28 days after treatment

Secondary Outcomes

Description: Marker for SARS-CoV-2

Measure: Time to SARS-CoV-2 RT-PCR negative

Time: Within 28 days after treatment

Description: The duration of a fever above 37.3 degrees Celsius

Measure: Duration of fever (Celsius)

Time: Within 28 days after treatment

Description: Marker for efficacy

Measure: Changes of blood oxygen (%)

Time: Within 28 days after treatment

Description: Marker for efficacy

Measure: Rate of all-cause mortality within 28 days

Time: Within 28 days after treatment

Description: Counts of lymphocyte in a litre (L) of blood

Measure: Lymphocyte count (*10^9/L)

Time: Within 28 days after treatment

Description: Alanine aminotransferase in unit (U)/litre(L)

Measure: Alanine aminotransferase (U/L)

Time: Within 28 days after treatment

Description: Creatinine in micromole (umol)/litre(L)

Measure: Creatinine (umol/L)

Time: Within 28 days after treatment

Description: Creatine kinase in U/L

Measure: Creatine kinase (U/L)

Time: Within 28 days after treatment

Description: C-reactive in microgram (mg)/litre(L)

Measure: C-reactive protein (mg/L)

Time: Within 28 days after treatment

Description: Procalcitonin in nanogram (ng)/litre(L)

Measure: Procalcitonin (ng/L)

Time: Within 28 days after treatment

Description: Lactate in millimole(mmol)/litre(L)

Measure: Lactate (mmol/L)

Time: Within 28 days after treatment

Description: IL-1beta in picogram(pg)/millilitre(mL)

Measure: IL-1beta (pg/mL)

Time: Within 28 days after treatment

Description: IL-2 in pg/mL

Measure: IL-2 (pg/mL)

Time: Within 28 days after treatment

Description: IL-6 in pg/mL

Measure: IL-6 (pg/mL)

Time: Within 28 days after treatment

Description: IL-8 in pg/mL

Measure: IL-8 (pg/mL)

Time: Within 28 days after treatment
3 Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19

The primary objective of the study is to evaluate the days until reaching clinical stability after starting randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury.

NCT04341038
Conditions
  1. COVID-19
  2. Lung Injury
Interventions
  1. Drug: Tacrolimus
  2. Drug: Methylprednisolone
MeSH:Lung Injury Wounds and Injuries

Primary Outcomes

Description: Assess the days until clinical stability is achieved after initiating randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury. Clinical stability is defined if all the following criteria are met for 48 consecutive hours: Body temperature ≤ 37.0ºC; PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300; Respiratory rate ≤ 24 rpm

Measure: Time to reach clinical stability

Time: 28 days

Secondary Outcomes

Description: days

Measure: Time to reach an afebrile state for 48 hours.

Time: 56 days

Description: days

Measure: Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300

Time: 56 days

Description: days

Measure: Time to reach FR ≤ 24 rpm for 48 hours

Time: 56 days

Description: days

Measure: Time to normalization of D-dimer (<250 ug / L)

Time: 56 days

Description: days

Measure: Time until PCR normalization (<5mg / L).

Time: 56 days

Description: days

Measure: Time until normalization of ferritin (<400ug / L)

Time: 56 days

Description: viral load

Measure: Study the impact of immunosuppressive treatment on viral load using quantitative PCR

Time: 56 days

Description: days

Measure: Time until hospital discharge

Time: 56 days

Description: days

Measure: Need for ventilatory support devices

Time: 56 days

Description: days

Measure: Duration that it is necessary to maintain ventilatory support.

Time: 56 days

Description: days

Measure: COVID-19 mortality

Time: 56 days

Description: days

Measure: all-cause mortality

Time: 56 days

Description: cytokines quantification technique by Luminex

Measure: Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission

Time: 56 days

Description: IDIBELL Clinical Research and Clinical Trials Unit will oversee the monitoring and pharmacovigilance

Measure: Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone.

Time: 56 days
4 SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

This study will the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

NCT04344184
Conditions
  1. COVID-19
  2. Lung Injury, Acute
  3. Kidney Injury
Interventions
  1. Drug: L-ascorbic acid
  2. Other: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: COVID disease status will be measured by the 9-point (from 0 to 8) World Health Organization (WHO) ordinal scale for disease improvement at 28 days.

Measure: Change in COVID disease status

Time: Baseline to 28, 60 and 90 days

Secondary Outcomes

Description: Change in serum oxalate levels

Measure: Renal safety biomarkers - serum oxalate

Time: On days 5,7 and 14

Description: Microscopic analysis of urine for presence of oxalate stones

Measure: Renal safety biomarkers - urine oxalate stones

Time: On days 5,7 and 14

Description: 24-hour urine oxalate levels

Measure: Renal safety biomarkers - 24-hour urine oxalate levels

Time: On days 5,7 and 14

Description: Renal-failure free days, with AKI defined by the KDIGO criteria

Measure: Acute Kidney Injury-free days

Time: On day 28, 90

Description: Mortality by all causes

Measure: Number of deaths

Time: On day 28, 60 and 90 days

Description: Difference in plasma ferritin levels in ng/mL, compared to baseline levels

Measure: Change in plasma ferritin levels

Time: Days 1-7 compared with baseline

Description: Difference in D-dimer levels in mcg/mL, compared to baseline levels

Measure: Change in plasma D-dimer levels

Time: Days 1-7 compared with baseline

Description: Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels

Measure: Change in serum lactate dehydrogenase (LDH) levels

Time: Days 1-7 compared with baseline

Description: Difference in plasma IL-6 levels in pg/mL, compared to baseline levels

Measure: Change in plasma IL-6 levels

Time: Days 1-7 compared with baseline

Description: Respiratory failure defined as resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation

Measure: Proportion of patients alive and free of respiratory failure

Time: At 28-days

Description: Percentage of patients alive and not requiring invasive mechanical ventilation

Measure: Proportion of patients alive and free of invasive mechanical ventilation

Time: At 28-days
5 A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.

NCT04350736
Conditions
  1. Acute Lung Injury (ALI) Associated With COVID-19
  2. Inflammatory Lung Conditions Associated With COVID-19
Interventions
  1. Drug: TD-0903
  2. Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events

Time: Day 1 to Day 8

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events

Time: Day 1 to Day 14

Secondary Outcomes

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC

Time: Day 1 through Day 9

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax

Time: Day 1 through Day 9

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax

Time: Day 1 through Day 9
6 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)

Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

NCT04351243
Conditions
  1. COVID-19
Interventions
  1. Drug: Gimsilumab
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

Primary Outcomes

Measure: Incidence of mortality

Time: Day 43

Secondary Outcomes

Measure: Incidence of subjects who are alive and not on mechanical ventilation

Time: Day 29

Description: Subjects who die will be assigned "0" ventilator-free days

Measure: Number of ventilator-free days

Time: Baseline to Day 29

Measure: Time to hospital discharge

Time: Baseline to Day 43
7 SOLIRIS® (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID 19) - An Expanded Access Program for Hospital-based Emergency Treatment

This protocol provides access to eculizumab treatment for participants with severe COVID-19.

NCT04355494
Conditions
  1. COVID-19
  2. Pneumonia, Viral
  3. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Interventions
  1. Biological: eculizumab
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

8 Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS A Single-arm, Open-label, Proof of Concept Study

The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of patients with COVID-19 severe pneumonia.

NCT04359290
Conditions
  1. ARDS, Human
  2. COVID
Interventions
  1. Drug: Ruxolitinib administration
MeSH:Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: To determine the efficacy of ruxolitinib measured by overall survival

Measure: Overall survival

Time: 28 days after registration into trial

Secondary Outcomes

Description: Assessment of the duration of ventilation support

Measure: Assessment of the duration of ventilation support

Time: registration until 90 days after registration into trial

Description: Assessment of the extent of cytokine storm reduction (IL-6, CRP, ferritin)

Measure: cytokine storm

Time: registration until 90 days after registration into trial

Description: To assess time on ICU

Measure: time on ICU

Time: registration until 90 days after registration into trial

Description: In order to classify the severity of the AEs, number of participants with treatment-related adverse events will be assessed by the "Common Terminology Criteria for Adverse Events" (CTCAE) version 5.0

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

Time: registration until 90 days after registration into trial

Description: To assess the timeframe for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG)

Measure: time frame for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG)

Time: registration until 90 days after registration into trial

Description: To asses the rates of flow (liter/minute), in order to detect possible amelioration of pulmonary function after Covid-19 infection

Measure: Rates of flow

Time: Discharge from hospital (end of treatment)

Description: To asses gas exchange (partial pressure of oxygen and carbon dioxide), in order to detect possible amelioration of pulmonary function after Covid-19 infection

Measure: Gas exchange

Time: Discharge from hospital (end of treatment)

Description: To assess forced expiratory volume in 1 second (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

Measure: Forced expiratory volume in 1 second (FEV1)

Time: Discharge from hospital (end of treatment)

Description: To assess forced vital capacity (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

Measure: Forced vital capacity (FVC)

Time: Discharge from hospital (end of treatment)

Description: To assess Tiffeneau-Pinelli index (FEV1/FVC ratio in %), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

Measure: Tiffeneau-Pinelli index

Time: Discharge from hospital (end of treatment)

Description: To determine the efficacy of ruxolitinib measured by overall survival

Measure: Overall survival

Time: 90 days after registration into trial
9 Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19

Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

NCT04360096
Conditions
  1. SARS-CoV 2
  2. COVID
  3. ARDS
  4. ALI
  5. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  6. Dyspnea
Interventions
  1. Drug: RLF-100 (aviptadil)
  2. Drug: Placebo
  3. Device: Nebulized administration of RLF-100 or Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Sy Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
HPO:Dyspnea Respiratory distress

Primary Outcomes

Description: Progression to ARDS is defined as the need for mechanical ventilation

Measure: Progression to ARDS

Time: 28 days

Secondary Outcomes

Description: Blood PO2 as measured by pulse oximetry

Measure: Blood oxygenation

Time: 28 days

Description: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity

Measure: RDP Dsypnea Scale

Time: 28 days

Description: Distance walked in six minutes

Measure: Distance walked in six minutes

Time: 28 days
10 A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared With Best Supportive Care in Patients With COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult patients with Coronavirus Disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Patients will be randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the patients) or BSC alone (1/3 of the patients). Best supportive care will consist of medical treatment and/or medical interventions per routine hospital practice.

NCT04369469
Conditions
  1. COVID-19 Severe Pneumonia
  2. Acute Lung Injury
  3. Acute Respiratory Distress Syndrome
  4. Pneumonia, Viral
Interventions
  1. Biological: Ravulizumab
  2. Other: Best Supportive Care
MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
HPO:Pneumonia

Primary Outcomes

Measure: Survival (based on all-cause mortality) at Day 29

Time: Baseline, Day 29

Secondary Outcomes

Measure: Number of days free of mechanical ventilation at Day 29

Time: Baseline, Day 29

Measure: Duration of intensive care unit stay at Day 29

Time: Baseline, Day 29

Measure: Change from baseline in Sequential Organ Failure Assessment at Day 29

Time: Baseline, Day 29

Measure: Change from baseline in SpO2/FiO2 at Day 29

Time: Baseline, Day 29

Measure: Duration of hospitalization at Day 29

Time: Baseline, Day 29

Measure: Survival (based on all-cause mortality) at Day 60 and Day 90

Time: Baseline, Day 60, Day 90
11 Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2

Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP could be promising COVID-19 infection- and lung injury preventing drug better than recombinant human ACE2 Mahmoud ELkazzaz1 1Department of chemistry and biochemistry, Faculty of Science, Damietta University, GOEIC, Egypt. _____________________________________________________________________________________________ _______________________________________________________________________ B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed the conversion of angiotensin II to angiotensin 1-7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. A study demonestrated that the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure. On the other hand, Treatment with recombinant human ACE2 protein (rhACE2), which is devoid of its membrane-anchored domain thus soluble, has been demonstrated to exhibit beneficial effects in various animal models including heart failure, acute lung injury, and diabetic nephropathy, and so forth. rhACE2 is currently tested in the clinic to treat ARDS and COVID-19 infected patients . Using cell cultures and organoids, researchers from the Karolinska Institutet in Sweden and the University of British Columbia (UBC) in Canada, showed that by adding a genetically modified variant of ACE2, called human recombinant soluble angiotensin-converting enzyme 2 (hrsACE2), COVID-19 was prevented from entering cells.The paper, published in Cell, shows that hrsACE2 had a dose dependent effect of viral growth of SARS-CoV-2 and was able to reduce it by a factor of 1,000 to 5,000 in cell cultures. Despite its beneficial effects, rhACE2 is a glycosylated protein and thus its preparation requires time- and cost-consuming protein expression system with mammalian or insect cells, which may not be advantageous in drug development and medical economy Although it had been reported that an immune response is associated with the chronic infusion of rhACE2 resulting in the degradation of rhACE226, this was not observed for B38-CAP; there were no antibodies against B38-CAP detectable in the serum of mice infused with B38-CAP for 2 weeks.B38-CAP is easily prepared with E. coli expression system and is cost effective. with therapeutic efficacy and less toxicity in mouse heart failure model. Implantation of B38-CAP-filled osmotic mini-pumps significantly suppressed Ang II-induced hypertension in conscious mice .without affecting the heart rate. These results indicate that B38-CAP antagonizes the vasopressor effect of Ang II. So the principle investigator expects and suggests that treating with cloned Bacterial ACE2 receptors -like enzyme of B38-CAP could be promising COVID-19 infection- and lung injury preventing drug better than recombinant human ACE2 in addition to brsACE2, expected to lure the virus to attach itself to the copy instead of the actual cells… It distracts the virus from infecting the cells to the same degree and should lead to a reduction in the growth of the virus in the lungs and other organs. A study showed that recombinant B38-CAP protein downregulates Ang II levels in mice and antagonizes Ang II-induced hypertension, pathological cardiac hypertrophy, and myocardial fibrosis. We also show beneficial effects of B38-CAP on the pathology of pressure overload-induced heart failure in mice without overt toxicities.Finally the principal investigator expect that treatment with ACE2-like enzyme in bacteria B38-CAP may be do the same mechanism of rhACE2 in inhibiting COVID -19 and the other suggested mechanism is that injection of ACE2-like enzyme of bacteria B38-CAP in human body may down regulate human ACE2 which is the real receptor of COVID -19 and in the same time it will be resistant to COVID- spike protein because there seems a difference in substrate specificity between two enzymes. Keywords: COVID 2019 ,Infection, B38-CAP , Bacterial ACE2 receptors -like enzyme , rhACE226.

NCT04375046
Conditions
  1. COVID-19
Interventions
  1. Drug: Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2)
MeSH:Infection Lung Injury

Primary Outcomes

Description: Compare the time course of body temperature (fever) between two groups over time.

Measure: Time course of body temperature (fever)

Time: 14 days

Description: Compare viral load between two groups over time.

Measure: Viral load over time

Time: 14 days

Secondary Outcomes

Description: PaO2/FiO2 ratio

Measure: P/F ratio over time

Time: 14 days

Description: SOFA, including assessment of respiratory, blood, liver, circulatory, nerve, kidney, from 0 to 4 scores in each systems, the higher scores mean a worse outcome.

Measure: Sequential organ failure assessment score(SOFA score) over time

Time: 14 days

Measure: Pulmonary Severity Index (PSI)

Time: 14 days

Description: Based on radiologist's assessment of inflammatory exudative disease, category as follows: significant improvement, partial improvement, no improvement, increase of partial exudation, significant increase in exudation, unable to judge.

Measure: Image examination of chest over time

Time: 14 days

Measure: Proportion of subjects who progressed to critical illness or death

Time: 14 days

Measure: Time from first dose to conversion to normal or mild pneumonia

Time: 14 days

Measure: T-lymphocyte counts over time

Time: 14 days

Measure: C-reactive protein levels over time

Time: 14 days

Measure: Angiotensin II (Ang II) changes over time

Time: 14 days

Measure: Angiotensin 1-7 (Ang 1-7) changes over time

Time: 14 days

Measure: Angiotensin 1-5 (Ang 1-5) changes over time

Time: 14 days

Measure: Renin changes over time

Time: 14 days

Measure: Aldosterone changes over time

Time: 14 days

Measure: Angiotensin-converting enzyme (ACE) changes over time

Time: 14 days

Measure: Angiotensin-converting enzyme 2 (ACE2) changes over time

Time: 14 days

Measure: Interleukin 6 (IL-6) changes over time

Time: 14 days

Measure: Interleukin 8 (IL-8) changes over time

Time: 14 days

Measure: Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time

Time: 14 days

Measure: Plasminogen activator inhibitor type-1 (PAI-1) changes over time

Time: 14 days

Measure: Von willebrand factor (vWF) changes over time

Time: 14 days

Measure: Tumor necrosis factor-α (TNF-α) changes over time

Time: 14 days

Measure: Soluble receptor for advanced glycation end products (sRAGE) changes over time

Time: 14 days

Measure: Surfactant protein-D (SP-D) changes over time

Time: 14 days

Measure: Angiopoietin-2 changes over time

Time: 14 days

Measure: Frequency of adverse events and severe adverse events

Time: 14 days
12 IbrutiNib in SARS CoV-2 Induced Pulmonary Injury and Respiratory Failure (iNSPIRE)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

NCT04375397
Conditions
  1. CoronaVirus Induced Disease-2019 (COVID-19)
Interventions
  1. Drug: Ibrutinib
  2. Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency Lung Injury

Primary Outcomes

Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

Measure: Percentage of Participants Alive and Without Respiratory Failure

Time: Day 28

Secondary Outcomes

Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).

Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline

Time: Day 14

Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.

Measure: Median Reduction in Days Spent on Supplemental Oxygen

Time: Up to Day 28

Description: Percentage of participants with mortality from any cause.

Measure: All-Cause Mortality

Time: Up to Day 28

Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

Measure: Percentage of Participants Experiencing Respiratory Failure or Death

Time: Up to Day 28

Description: Percentage of participants alive and not requiring mechanical ventilation.

Measure: Mechanical Ventilation-Free Survival

Time: Up to Day 56

Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.

Measure: Days on Mechanical Ventilation

Time: Up to Day 56

Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.

Measure: Duration of hospitalization

Time: Up to Day 56

Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.

Measure: Time to Discharge

Time: Up to Day 56

Description: PaO2:FiO2 ratio is an index of respiratory distress.

Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio

Time: Up to Day 56

Description: Oxygenation Index is a parameter of pulmonary function of participants.

Measure: Oxygenation Index

Time: Up to Day 56

Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Measure: Number of Participants With Adverse Events

Time: Up to Day 56

Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Measure: Number of Participants With Abnormal Laboratory Findings

Time: Up to Day 56
13 Pulmonary and Motor Rehabilitation for People With COVID-19 in Intensive Care Units to Reduce Length of Stay in Hospital

COVID-19 DISEASE Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, severe acute respiratory syndrome from COVID-19, that was first recognized in Wuhan, China, in December 2019. While most people with COVID-19 develop mild or uncomplicated illness, approximately 14% develop severe disease requiring hospitalization and oxygen support and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by acute respiratory disease syndrome (ARDS) requiring prolonged mechanical ventilation, sepsis and septic shock, multiorgan failure, including acute kidney, liver and cardiac injury. ARDS REHABILITATION Critically ill people who undergo prolonged mechanical ventilation often develop weakness, with severe symmetrical weakness of and deconditioning of the proximal musculature and of the respiratory muscles (critical illness neuropathy/myopathy).These individuals also develop significant functional impairment and reduced health-related quality of life (HRQL) up to 2 and 5 years after discharge. ARDS survivors may complain of depression, anxiety, memory disturbances, and difficulty with concentration often unchanged at 2 and 5 years. Less than half of all ARDS survivors return to work within the first year following discharge, two-thirds at two years, and more than 70% at five years. Early physiotherapy (PT) of people with ARDS has recently been suggested as a complementary therapeutic tool to improve early and late outcomes. The aims of PT programs should be to reduce complications of immobilization and ventilator-dependency, to improve residual function, to prevent new hospitalisations, and to improve health status and HRQL. Physiotherapy in critical patients is claimed also to prevent and contribute to treat respiratory complications such as secretion retention, atelectasis, and pneumonia. Early mobilization and maintenance of muscle strength may reduce the risk of difficult weaning, limited mobility, and ventilator dependency. Lastly, pulmonary rehabilitation in ICU in mechanically ventilated subjects may reduce length of stay in ICU up to 4.5 day, shorten mechanical ventilation of 2.3 days and weaning by 1.7 days. The aim of this study is to investigate how early pulmonary and motor rehabilitation impacts on length of hospital admission (ICU and acute ward) and early and late outcomes inpatients that develop ARDS due to COVID-19.

NCT04381338
Conditions
  1. Corona Virus Disease 19 (COVID-19)
  2. COVID
  3. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  4. Critical Illness
Interventions
  1. Other: Pulmonary and Motor Rehabilitation
MeSH:Virus Diseases Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Critical Illness

Primary Outcomes

Description: days of ICU stay

Measure: Length of ICU stay

Time: up to 60 days

Secondary Outcomes

Description: days of hospital stay

Measure: Length of hospital stay

Time: up to 90 days
14 Combination of Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP and Isotretinoin Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2

Combination of Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP and Isotretinoin Could be Promising COVID-19 Infection- and Lung Injury Preventing Drug Better Than Recombinant Human ACE2 Mahmoud ELkazzaz1 1Department of chemistry and biochemistry, Faculty of Science, Damietta University, GOEIC, Egypt. _____________________________________________________________________________________________ ________________________________________________________________________ B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. A study demonstrated that the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure. pretreatment of B38-CAP markedly down regulated a massive increase of plasma Ang II levels at 5 min after Ang II injection In addition to the currently used drugs to inhibit Ang II generation or signaling, such as ACE inhibitors or Angiotensin receptor blockers, direct down-modulation of Ang II levels by rhACE2 protein is one of the promising candidates for new therapeutic strategy in cardiovascular disease and other Ang II-related diseases, e.g. ARDS. On the other hand, although mass production of rhACE2 as a protein drug costs due to requirement of mammalian cell expression systems, B38-CAP is easily prepared with E. coli expression system and is cost effective. Therapeutic efficacy and less toxicity in mouse heart failure models would warrant further investigation of B38-CAP or other microbial carboxypeptidases in disease models. Finally the principal investigator expects that treatment with ACE2-like enzyme of bacteria B38-CAP expected to work efficiently Like human ACE2 and it will save the lung cells from COVID - 19 inhibitory effect and down regulation of ACE2 because COVID-19 binds to human ACE2 and down regulates it and this receptors is very important for lung cells survival and function So ,the principal investigator also expects that B38-CAP ACE2 like enzyme may be not recognized by COVID -19 spike protein because evolutionary it is too far away from human ace2 and human ACE2 is a real receptor of COVID -19 not ACE2 like enzyme but in the same time it will make the same function of human ACE2 In another study by Sinha et al who analyzed a publicly available Connectivity Map (CMAP) dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules, isotretinoin was the strongest down-regulator of ACE 2 receptors. On the other hand, they found 6 drugs in CMAP that are currently being investigated in clinical trials for treating COVID-19 (chloroquine, thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov), none of which was found to significantly alter ACE2 expression (P>0.1) Moreover, another study demonstrated that isotretinoin is a Potential papain like protease (PLpro) inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening . So, the principal investigator expects strong inhibition of COVID - 19 infection And rescuing the lung cells from its serious attack by treating with ACE2 like enzyme and Isotretinoin Keywords: COVID 2019 , Isotretinoin,B38-CAP , Bacterial ACE2 receptors -like enzyme , rhACE226.

NCT04382950
Conditions
  1. COVID
Interventions
  1. Combination Product: Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) plus Aerosolized 13 cis retinoic acid
MeSH:Lung Injury

Primary Outcomes

Description: Compare the time course of body temperature (fever) between two groups over time.

Measure: Time course of body temperature (fever)

Time: at 14 days

Secondary Outcomes

Description: Compare viral load between two groups over time.

Measure: Viral load over time

Time: 14 days

Description: PaO2/FiO2 ratio

Measure: P/F ratio over time

Time: 14 days

Description: SOFA, including assessment of respiratory, blood, liver, circulatory, nerve, kidney, from 0 to 4 scores in each systems, the higher scores mean a worse outcome.

Measure: Sequential organ failure assessment score(SOFA score) over time

Time: 14 days

Measure: Pulmonary Severity Index (PSI)

Time: 14 days

Description: Based on radiologist's assessment of inflammatory exudative disease, category as follows: significant improvement, partial improvement, no improvement, increase of partial exudation, significant increase in exudation, unable to judge.

Measure: Image examination of chest over time

Time: 14 days

Measure: Proportion of subjects who progressed to critical illness or death

Time: at 14 days

Measure: Time from first dose to conversion to normal or mild pneumonia

Time: 14 days

Measure: T-lymphocyte counts over time

Time: 14 days

Measure: C-reactive protein levels over time

Time: 14 days

Measure: Angiotensin II (Ang II) changes over time

Time: 14 days

Measure: Angiotensin 1-7 (Ang 1-7) changes over time

Time: 14 days

Measure: Angiotensin 1-5 (Ang 1-5) changes over time

Time: 14 days

Measure: Renin changes over time

Time: 14 days

Measure: Aldosterone changes over time

Time: 14 days

Measure: Angiotensin-converting enzyme (ACE) changes over time

Time: 14 days

Measure: Interleukin 6 (IL-6) changes over time

Time: 14 days

Measure: Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time

Time: 14 days

Measure: Plasminogen activator inhibitor type-1 (PAI-1) changes over time

Time: 14 days

Measure: Von willebrand factor (vWF) changes over time

Time: 14 days

Measure: Tumor necrosis factor-α (TNF-α) changes over time

Time: 14 days

Measure: Soluble receptor for advanced glycation end products (sRAGE) changes over time

Time: 14 days

Measure: Surfactant protein-D (SP-D) changes over time

Time: 14 days

Measure: Frequency of adverse events and severe adverse events

Time: 14 days
15 A Multicenter, Single-Treatment Study to Assess the Safety and Preliminary Efficacy of Lyophilized Lucinactant in Adults With COVID-19 Associated Acute Lung Injury

This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment.

NCT04389671
Conditions
  1. COVID-19
  2. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Interventions
  1. Drug: Lucinactant
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

Primary Outcomes

Description: The AUC for OI through 12 hours measured using the trapezoidal method, where OI is defined as mean airway pressure (Paw)×fraction of inspired oxygen (FiO2)×100/arterial pressure of oxygen (PaO2)

Measure: Oxygenation index (OI) area under the curve (AUC)0-12

Time: 12 hours post initiation of dosing

Secondary Outcomes

Description: FiO2 change from baseline

Measure: FiO2

Time: 24 hours post initiation of dosing

Description: PaO2 change from baseline

Measure: PaO2

Time: 24 hours post initiation of dosing

Description: SpO2 change from baseline

Measure: Oxygenation from pulse oximetry (SpO2)

Time: 24 hours post initiation of dosing

Description: Change from baseline in P/F ratio, defined as PaO2/FiO2

Measure: P/F ratio

Time: 24 hours post initiation of dosing

Description: Change from baseline in VI, defined as [respiration rate (RR)×(peak inspriatory pressure [PIP] - peak expiratory end pressure [PEEP])× arterial pressure of carbon dioxide (PaCO2)]/1000

Measure: Ventilation Index (VI)

Time: 24 hours post initiation of dosing

Description: Change from baseline in lung compliance, as measured by the ventilator

Measure: Lung compliance

Time: 24 hours post initiation of dosing
16 A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure

A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.

NCT04389840
Conditions
  1. COVID-19
  2. Acute Lung Injury
  3. SARS-CoV-2
Interventions
  1. Drug: Dociparastat sodium
  2. Drug: Placebo
MeSH:Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Alive and free of invasive mechanical ventilation

Measure: Proportion of participants who are alive and free of invasive mechanical ventilation

Time: Through Day 28

Secondary Outcomes

Description: Time to all-cause mortality

Measure: All-cause mortality

Time: Through Day 28
17 Lung CT Scan Analysis of SARS-CoV2 Induced Lung Injury by Machine Learning: a Multicenter Retrospective Cohort Study.

This is a multicenter observational retrospective cohort study that aims to study the morphological characteristics of the lung parenchyma of SARS-CoV2 positive patients identifiable in patterns through artificial intelligence techniques and their impact on patient outcome.

NCT04395482
Conditions
  1. covid19
Interventions
  1. Other: Lung CT scan analysis in COVID-19 patients
MeSH:Lung Injury

Primary Outcomes

Description: Describe the parenchymal lung damage induced by COVID-19 through a qualitative analysis with chest CT through artificial intelligence techniques.

Measure: A qualitative analysis of parenchymal lung damage induced by COVID-19

Time: Until patient discharge from the hospital (approximately 6 months)

Description: Describe the parenchymal lung damage induced by COVID-19 through a quantitative analysis with chest CT through artificial intelligence techniques.

Measure: A quantitative analysis of parenchymal lung damage induced by COVID-19

Time: Until patient discharge from the hospital (approximately 6 months)

Secondary Outcomes

Description: The potential impact of parenchymal morphological CT scans in patients with severe moderate respiratory failure assessed as intensive care mortality.

Measure: The potential impact of parenchymal morphological CT scans in patients with severe moderate respiratory failure.

Time: Until patient discharge from the hospital (approximately 6 months)

Description: The potential impact of parenchymal morphological CT scans in patients with severe moderate respiratory failure assessed as hospital mortality.

Measure: The potential impact of parenchymal morphological CT scans in patients with severe moderate respiratory failure.

Time: Until patient discharge from the hospital (approximately 6 months)

Description: The potential impact of parenchymal morphological CT scans in patients with severe moderate respiratory failure assessed as days free from mechanical ventilation.

Measure: The potential impact of parenchymal morphological CT scans in patients with severe moderate respiratory failure.

Time: Until patient discharge from the hospital (approximately 6 months)

Description: The hypothesis is that the uso of deep neural network models for lung segmentation in Acute Respiratory Distress Syndrome (ARDS) in animal models and Chronic Obstructive Pulmonary Disease (COPD) in patients that could be applied to self-segment the lungs of COVID-19 patients through a learning transfer mechanism with artificial intelligence.

Measure: Automated segmentation of lung scans of patients with COVID-19 and ARDS.

Time: Until patient discharge from the hospital (approximately 6 months)

Description: Expand the knowledge of chest CT features in COVID-19 patients and their detail through the use of machine learning and other quantitative techniques comparing CT patterns of COVID-19 patients to those of patients with ARDS.

Measure: Knowledge of chest CT features in COVID-19 patients and their detail through the use of machine learning and other quantitative techniques.

Time: Until patient discharge from the hospital (approximately 6 months)

Description: Determine the capacity within which the artificial intelligence analysis that uses deep learning models can be used to predict clinical outcomes from the analysis of the characteristics of the chest CT obtained within 7 days of hospital admission; combining quantitative CT data with clinical data.

Measure: The ability within which the analysis of artificial intelligence that uses deep learning models can be used to predict clinical outcomes

Time: Until patient discharge from the hospital (approximately 6 months)
18 Nebulized Heparin vs. Placebo for the Treatment of COVID-19 Induced Lung Injury

Randomized, placebo controlled study to determine if nebulized heparin may reduce the severity of lung injury caused by the novel coronavirus, also known as COVID-19

NCT04397510
Conditions
  1. Covid-19
  2. ARDS, Human
  3. Acute Lung Injury
Interventions
  1. Drug: Heparin
  2. Drug: 0.9% Sodium-chloride
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Measure: Mean daily PaO2 to FiO2 ratio

Time: 10 days

Secondary Outcomes

Measure: Duration of mechanical ventilation

Time: 30 days

Measure: ICU length of stay

Time: 30 days

Measure: Mortality Rate

Time: 30 days

Measure: Incidence of adverse drug events

Time: 10 days
19 Treatment of Lung Injury From COVID-19 Infection With Intravenous Sodium Nitrite: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Study

This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Nitrite Injection for treatment of patients infected with COVID-19 who develop lung injury and require mechanical ventilation.

NCT04401527
Conditions
  1. COVID-19
  2. Acute Respiratory Distress Syndrome
  3. Acute Respiratory Failure
Interventions
  1. Drug: Sodium Nitrite
  2. Drug: Normal Saline
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury

Primary Outcomes

Description: Proportion of study subjects who are alive and free of respiratory failure at Day 28

Measure: Survival with Unassisted Breathing

Time: Day 28

Secondary Outcomes

Description: Number of days alive without mechanical ventilation from start of study through Day 28

Measure: Survival without Mechanical Ventilation

Time: Day 28

Description: Number of days alive and not in the intensive care unit from start of study through Day 28.

Measure: Survival without Intensive Care

Time: Day 28

Description: Number of days alive and not in hospital from start of study through Day 28.

Measure: Survival without Hospitalization

Time: Day 28

Description: Alive on Day 28 and no use of ECMO therapy any time between start of study and Day 28.

Measure: Survival without ECMO

Time: Day 28

Description: Alive on Day 28

Measure: Survival

Time: Day 28

Other Outcomes

Description: Oxygenation index (PaO2/FIO2) at Day 14

Measure: Lung Status

Time: Day 14

Description: Blood urea nitrogen (BUN) at Day 14

Measure: Kidney Status (1)

Time: Day 14

Description: Creatinine at Day 14

Measure: Kidney Status (2)

Time: Day 14

Description: Liver function tests (ALT and AST) at Day 14

Measure: Liver Status

Time: Day 14
20 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19

This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.

NCT04402866
Conditions
  1. Acute Lung Injury (ALI) Associated With COVID-19
  2. Lung Inflammation Associated With COVID-19
Interventions
  1. Drug: TD-0903
  2. Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Pneumonia Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Number of Respiratory Failure-Free Days (RFDs) from randomization through Day 28

Measure: Part 2: Respiratory Failure-Free Days (RFDs)

Time: Baseline through Day 28

Secondary Outcomes

Description: Proportion of subjects in each category of the 8-point Clinical Status scale. The Clinical Status scale contains 8 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized, no limitations on activities') to 8 (representing 'Death'). The various measures describe hospitalization status and the various limitations and requirements for oxygen support.

Measure: Part 2: Clinical Status Scale

Time: Day 7, 14, 21 and 28

Description: Proportion of subjects alive and respiratory failure-free on Day 28

Measure: Part 2: Subjects alive and respiratory failure-free

Time: Day 28

Description: Change from baseline in SaO2/FiO2 ratio on Day 7

Measure: Part 2: SaO2/FiO2 ratio

Time: Baseline, Day 7
21 A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID 19 Pneumonia and Acute Lung Injury

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT, for the treatment of patients with COVID-19 pneumonia who have mild to moderate ARDS. LIGHT is a cytokine in the TNF super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

NCT04412057
Conditions
  1. COVID-19 Pneumonia
  2. Acute Lung Injury
  3. ARDS
Interventions
  1. Drug: CERC-002
  2. Drug: Placebo
MeSH:Pneumonia Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
HPO:Pneumonia

Primary Outcomes

Description: Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation

Measure: Proportion of patient alive and free of respiratory failure

Time: Baseline to Day 28

Secondary Outcomes

Description: 1-month mortality

Measure: Proportion of subjects who are alive

Time: Baseline to Day 28
22 Knowledge, Attitude and Practice About COVID-19 and Awareness of Infection Control to Prevent COVID-19 Transmission in Clinics and Perception About Online Learning During Lock Down Period: A Cross-sectional Study

Coronavirus disease 2019 (abbreviated "COVID- 19") is a pandemic respiratory disease that is caused by a novel coronavirus and was first detected in December 2019 in Wuhan, China. The disease is highly infectious, and its main clinical symptoms include fever, dry cough, fatigue, myalgia, and dyspnoea.1 In China, 18.5% of the patients with COVID-19 developed to the severe stage, which is characterized by acute respiratory distress syndrome, septic shock, difficult-to-tackle metabolic acidosis, and bleeding and coagulation dysfunction. After China, COVID-19 spread across the world and many governments implemented unprecedented measures like suspension of public transportation, the closing of public spaces, close management of communities, and isolation and care for infected people and suspected cases. The Malaysian government had enforced Movement Control Order (MCO) from 18th March to 4th May 2020 and henceforth Conditional Movement Control Order (CMCO) until 9th June 2020. The battle against COVID-19 is still continuing in Malaysia and all over the world. Due to the CMO and CMCO in the country, public and private universities have activated the e-learning mode for classes and as the government ordered, universities are closed and no face-to-face activities allowed. This has forced students of all disciplines including dentistry to stay at home which are wide-spread across Malaysia and shift to e- learning mode. To guarantee the final success for fight against COVID-19, regardless of their education status, students' adherence to these control measures are essential, which is largely affected by their knowledge, attitudes, and practices (KAP) towards COVID-19 in accordance with KAP theory. Once the restrictions are eased students have to come back and resume their clinical work in the campus. Hence, in this study we assessed the Knowledge, Attitude, and Practice (KAP) towards COVID-19 and the students preference for online learning.

NCT04449081
Conditions
  1. Acute Respiratory Distress Syndrome
  2. Corona Virus Infection
  3. Acute Lung Injury
  4. Fever
  5. Myalgia
  6. Cough
  7. Dyspnea
  8. Septic Shock
  9. Bleeding
Interventions
  1. Behavioral: Knowledge, Attitude, Practice, Awareness, Preference
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Myalgia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
HPO:Dyspnea Myalgia Respiratory distress

Primary Outcomes

Description: KAP towards COVID-19 was assessed using validated questionnnaire

Measure: Knowledge, Attitude, Practice of dental students towards COVID-19

Time: 4 months

Secondary Outcomes

Description: Awareness level about Infection control to prevent COVID-19 transmission in clinics was assesed using a standardized questionnaire

Measure: Awareness level about Infection control to prevent COVID-19 transmission in clinics

Time: 4 months

Description: Preference towards online learning. was assessed using a standard questionnaire

Measure: Preference towards online learning.

Time: 4 months
23 Adjuvant Therapeutic Effects of Melatonin Agonist on Hospitalized Patients With Confirmed or Suspected COVID-19

COVID-19 is impacting on health systems in Brazil and worldwide. Reducing the risk of clinical deterioration and prolonged disease duration in hospitalized patients with COVID-19 may alleviate the burden caused by the pandemic. Melatonin (N-acetyl-5-methoxytryptamine) has demonstrated antiapoptotic, antioxidative, and anti-inflammatory roles and has been suggested as a potential protector against organ injuries and even mediate lower mortality rates after polymicrobial sepsis in animal models. Melatonin agonists may modulate protective effects against acute lung injury and play a clinical role in individuals with SARS-CoV-2 infection. The investigators proposed a clinical trial testing the effects of ramelteon 8mg in hospitalized patients with COVID-19.

NCT04470297
Conditions
  1. Covid19
  2. Lung Injury
Interventions
  1. Drug: Ramelteon 8mg
MeSH:Lung Injury

Primary Outcomes

Description: Defined as a National Early Warning Score 2 (NEWS2) of 0 maintained for 24 hours [Time Frame: Assessed daily (enrollment is day 0)] The NEWS consists of a simple aggregate scoring system based on physiological measurements, regularly registered in inpatient settings, including six parameters: respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new confusion, and temperature.

Measure: Time to resolution of symptoms [National Early Warning Score 2 (NEWS2) of 0]

Time: enrollment is day 0

Secondary Outcomes

Description: Critical COVID-19 illness as a composite of admission to the intensive care unit (ICU), invasive ventilation, or death

Measure: Clinical worsening to critical COVID-19 illness

Time: until Day 30

Description: Measured by duration of use of supplemental oxygen (if applicable)

Measure: Duration of supplemental oxygen therapy

Time: until day 14

Description: Measured by duration of use of mechanical ventilation

Measure: Duration of mechanical ventilation (if applicable)

Time: until day 30

Description: Measured by duration of hospitalization

Measure: Duration of hospitalisation

Time: until day 30

Description: Presence or absence of SARS-CoV-2 Viral RNA in nasopharyngeal swab or lower respiratory secretions

Measure: Proportion of participants with virologic clearance in nasopharyngeal swab RT-PCR

Time: Day 14

Description: Reduction of C-reactive protein levels > 50% in comparison with PCR levels at the admission

Measure: C-reactive protein (CRP) level's reduction

Time: Days 3, 5 and 8

Description: Incidence of new onset lymphopenia during hospitalization measured by blood draw

Measure: Incidence of New Onset Lymphopenia

Time: Through study completion, average of 15 days

Description: Reduction of mean direct bilirubin levels in comparison with levels at the admission

Measure: Direct bilirubin level's reduction

Time: Measured in study Days 3, 5, and 8

Description: Differences in number of patients in study arms who experienced side effects

Measure: Side Effects

Time: until day 14
24 Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.

NCT04482712
Conditions
  1. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
  2. Respiratory Failure
  3. Sars-CoV2
Interventions
  1. Drug: Rapamycin
  2. Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury Syndrome

Primary Outcomes

Description: The proportion of participants who survive without respiratory failure

Measure: Survival rate

Time: 4 weeks

Secondary Outcomes

Description: The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8

Measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale

Time: Baseline to 4 weeks

Description: An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)

Measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale

Time: Baseline to 4 weeks

Other Outcomes

Description: Total number of deaths during the study period

Measure: All cause mortality

Time: 4 weeks

Description: Number of days on ECMO

Measure: Duration of ECMO

Time: Up to 4 weeks

Description: Number of days participants are on supplemental oxygen

Measure: Duration of supplemental oxygen

Time: Up to 4 weeks

Description: Days of hospitalization

Measure: Length of hospital stay

Time: Up to 4 weeks

Description: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)

Measure: Length of time to SARS-CoV2 negativity

Time: Up to 4 weeks
25 Pulmonary Tomographic Findings in COVID-19 and Influenza H1N1 Patients at IMSS Guanajuato

The investigators decided to conduct a longitudinal study that compares the pulmonary tomographic patterns found in patients with viral pneumonia (i.e. influenza H1N1 and SARS-CoV-2) at a regional hospital. The primary aim of this study is to evaluate the association between the radiological CT pattern and the need for invasive mechanical ventilation. A secondary aim is to assess the mortality within the first 28 days of intensive care unit admission.

NCT04499378
Conditions
  1. Covid19
  2. Influenza A H1N1
  3. Intubation Complication
  4. Morality
  5. Lung Injury, Acute
Interventions
  1. Diagnostic Test: Lung CT
MeSH:Influenza, Human Lung Injury Acute Lung Injury

Primary Outcomes

Description: Need for oral intubation within the first 10 days.

Measure: Oral intubation

Time: 10 days

Secondary Outcomes

Description: 28-day survival analysis using the Kaplan Meyer and Cox regression models.

Measure: Survival

Time: 28 days
26 Exhaled Breath Particles as a Clinical Indicator for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrom (ARDS) in COVID-19 Positive and Negative Patients

Acute Respiratory Distress Syndrome (ARDS) reflects the hallmark of the critical course of COVID19. We have recently shown that Exhaled Breath Particles (EBP) measured as particle flowrate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR increased before the cytokine storm. Early detection of ALI and ARDS is crucial for the patient's chance of survival as early treatment, such as preparing for intensive care, prone position and protective ventilation when the patient is treated in mechanical ventilation, can be implemented early in the process. In the present study we aim to use real time PFR as an early detector for COVID19 induced ARDS. We will also collect EBPs onto a membrane for subsequent molecular analysis. Previous studies have shown that most of those proteins found in broncho alveolar lavage (BAL) are also found in EBP. We therefore also aim to be able to diagnose COVID19 by analyzing EBP using PCR with the same specificity as PCR from BAL, but also to identify protein biomarkers for early detection of ARDS.

NCT04503057
Conditions
  1. Covid19
  2. ARDS, Human
  3. ALI
MeSH:Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Detect COVID-19 in EBP using RT-PCR

Measure: COVID-19 RT-PCR detection in EBP

Time: 12-36 months

Description: Detection of proteins biomarkers in EBP

Measure: Detection of proteins biomarkers in EBP

Time: 12-36 months

Description: We have recently shown that Exhaled Breath Particles (EBP) measured as particle flowrate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR increased before the cytokine storm. Early detection of ALI and ARDS is crucial for the patient's chance of survival as early treatment, such as preparing for intensive care, prone position and protective ventilation when the patient is treated in mechanical ventilation, can be implemented early in the process. In the present study we aim to use real time PFR as an early detector for COVID19 induced ARDS.

Measure: Particle flow rate as an early indicator for lung injury

Time: 12-36 months
27 Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Mechanical Ventilation in Ireland

Existing information suggests that a drug called heparin, given through a device called a nebuliser, will decrease severity of lung damage caused by COVID-19 who require the assistance of a ventilator to breathe. It is thought that heparin could do this through multiple mechanisms. The investigators will measure the effect with a marker called d-dimer, which is related to blood clotting, and monitor the safety of this treatment as one of the major outcomes for the study. The investigators will also assess clinical outcomes such as markers of oxygen levels, time to liberation from a ventilator in patients with COVID-19 lung disease, and functional outcomes at day 28 and 60 as secondary outcomes.

NCT04511923
Conditions
  1. Covid19
  2. ARDS, Human
  3. Lung Injury, Acute
  4. Ventilation Perfusion Mismatch
Interventions
  1. Drug: Nebulised heparin
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: Effect of nebulised heparin on d-dimer profile, assessed via d-dimer AUC and via a mixed effects model, with data collected on days 1, 3, 5 and 10.

Measure: D-dimer profile

Time: Up to day 10.

Description: Safety of nebulised heparin delivered by aerogen solo nebuliser in patients with COVID-19 induced severe respiratory failure, as measured by the incidence of severe adverse events.

Measure: Frequenccy of Severe Adverse Outcomes

Time: Up to day 60

Secondary Outcomes

Description: Determine the impact of nebulised heparin on oxygenation index

Measure: Oxygenation Index

Time: Up to day 10

Description: Effect of nebulised heparin on indices of inflammation (Interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1), C-reactive protein, procalcitonin, Ferritin,) will be assessed (AUC on days 1, 3, 5 and 10)

Measure: Indices of Inflammation

Time: Up to day 10

Description: Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed.

Measure: Ratios of Indices of Inflammation

Time: Up to day 10

Description: Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10).

Measure: Indices of Coagulation

Time: Up to day 10

Description: Determine the effect of nebulised heparin on Quasi-Static Lung Compliance (i.e. tidal volume/(Plateau pressure-PEEP) measured on days 1,3,5,10.

Measure: Quasi-Static Lung Compliance

Time: Up to day 10

Description: Time to separation from invasive ventilation, where non survivors are treated as though not separated from invasive ventilation.

Measure: Time to separation from invasive ventilation

Time: Up to day 28

Description: Number treated with neuromuscular blockers instituted after enrolment

Measure: Number treated with neuromuscular blockers

Time: Up to day 10

Description: Number treated with prone positioning instituted after enrolment

Measure: Number treated with Prone positioning

Time: Up to day 10

Description: Number treated with extra-corporeal membrane oxygenation instituted after enrolment

Measure: Number treated with extra-corporeal membrane oxygenation

Time: Up to day 10

Description: Number tracheotomised

Measure: Number requiring Tracheostomy

Time: Up to day 28

Description: Time to separation from invasive ventilation among survivors

Measure: Time to separation from invasive ventilation among survivors

Time: Up to day 28

Description: Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care

Measure: Discharge to ward

Time: Up to day 28

Description: Time to discharge from the ICU to day 28, among survivors

Measure: Discharge to ward in survivors

Time: Up to day 28

Description: Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60

Measure: Patient Survival

Time: Up to day 60

Description: Number residing at home or in a community setting at day 60

Measure: Number of patients residing at home or in a community setting at day 60

Time: Up to day 60

Description: Number residing at home or in a community setting at day 60, among survivors

Measure: Number of surviving patients residing at home or in a community

Time: Up to day 60
28 A Proof of Concept Study of the Safety and Efficacy of VIB7734 for the Treatment and Prevention of Acute Lung Injury (ALI) in Patients With SARS-CoV-2 Infection

The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.

NCT04526912
Conditions
  1. Acute Lung Injury
Interventions
  1. Drug: VIB7734
  2. Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: Critical illness is defined by respiratory failure (requiring any of the following: endotracheal intubation, oxygen delivered by high flow nasal cannula, non-invasive positive pressure ventilation, extracorporeal membrane oxygenation or clinical diagnosis of respiratory failure) or shock (systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg, or requiring vasopressors)

Measure: The proportion of patients who achieve treatment success through Day 28, defined as avoidance of death and critical illness

Time: Day 1 (Baseline) through Day 28

Secondary Outcomes

Description: Defined as measure of safety

Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent fatal and life-threatening SAEs, Treatment-emergent Serious Adverse Events

Time: Day 1 (Baseline) through Day 70

Description: Safety evaluation via review of labs (white blood cell (WBC) with differential counts, hemoglobin, platelet count, liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin levels), serum chemistry, cardiac troponin coagulation markers (prothrombin time [PT], partial thromboplastin time [PTT], D dimer, fibrinogen), and urinalysis)

Measure: Change in safety laboratory parameters

Time: Day 1 (Baseline) through Day 70
29 A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

NCT04574869
Conditions
  1. Acute Lung Injury
  2. ALI
  3. COVID-19
Interventions
  1. Drug: RLS-0071
  2. Drug: RLS-0071
  3. Drug: Placebo
  4. Drug: RLS-0071
  5. Drug: RLS-0071
  6. Drug: Placebo
MeSH:Pneumonia Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
HPO:Pneumonia

Primary Outcomes

Measure: Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.

Time: Through study completion at Day 28 following last dose.

Secondary Outcomes

Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose apparent total body clearance for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

Time: Through study completion at Day 28 following last dose.

Measure: Overall survival.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.

Time: Days on ventilation while in the hospital through study completion at Day 28.

Measure: Incidence of transfer to the ICU.

Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.

Measure: Duration of hospitalization after treatment (days).

Time: Through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

Time: Through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

Time: Through study completion at Day 28 following last dose.

Measure: Duration of requirement for supplemental oxygen after treatment (days).

Time: Through study completion at Day 28 following last dose.

Measure: PaO2/FiO2

Time: Through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Description: Dialysis will be assessed by the investigator with CTCAE's latest version.

Measure: Incidence and duration after treatment (days) of dialysis.

Time: Through Day 15 and through study completion at Day 28 following last dose.

Measure: Levels of complement activity (eg, CH50).

Time: Through study completion at Day 28 following last dose.

Measure: Levels of C1q (free and bound to RLS-0071).

Time: Through study completion at Day 28 following last dose.
30 Remote Ischemic Conditioning as an Adjunct Therapy for Severe COVID-19 Disease: a Prospective Randomized Pilot Study

This research aims to assess the use of an experimental and non-invasive procedure, Remote Ischemic Conditioning (RIC), as an adjunct therapy in attenuating severe COVID-19 disease. An excessive and counterproductive systemic inflammatory response is thought to be a major cause of severe disease and death in patients with COVID-19. Severe ICU cases frequently have markedly higher levels of inflammatory markers such as CRP, IL-6, IL and TNF-a; which is thought to be correlated with increasing disease severity. The relationship between dysregulated inflammatory processes and disease states such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are well understood. ALI is characterized by an acute exaggerated mononuclear/neutrophilic inflammatory response followed by progressive collagen deposition in the lung, and if severe enough, may progress to ARDS requiring ventilation.

NCT04659460
Conditions
  1. COVID
  2. Corona Virus Infection
  3. Acute Lung Injury
  4. Ischemia Limb
  5. Acute Respiratory Distress Syndrome
Interventions
  1. Device: Remote Ischemic Conditioning
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

Primary Outcomes

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Interleukin 1-Beta (IL-1B) (pg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Interleukin 6 (IL-6) (pg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: C-reactive protein (CRP) (mg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Tumour Necrosis Factor Alpha (TNFa) (pg/mL)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Neutrophil to Lymphocyte Ratio (NLR) (absolute neutrophils/lymphocytes)

Time: Through study completion - up to 12 months

Description: Serum concentration, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Serum Ferritin (ng/mL)

Time: Through study completion - up to 12 months

Description: Standard coagulation parameter, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: International Normalized Ratio (INR)

Time: Through study completion - up to 12 months

Description: Standard coagulation parameter, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point)

Measure: Prothrombin Time (PTT)

Time: Through study completion - up to 12 months

Description: ROTEM coagulation assessment using the commercial ROTEM device traditionally used for the assessment of coagulopathy, to be collected immediately before RIC treatment, treatment plus 6 hours, treatment plus 12 hours, treatment plus 24 hours, and treatment plus 48 hours (+/- 1 hour at each 0+ time point).

Measure: Rotational Thromboelastometry (ROTEM)

Time: Through study completion - up to 12 months

Secondary Outcomes

Description: Number of continuous calendar days or partial calendar days including treatment with invasive ventilation.

Measure: Total duration of mechanical ventilation (number of days)

Time: Through study completion - up to 12 months

Description: Number of continuous calendar days or partial calendar days admitted to an acute care hospital.

Measure: Intensive Care Unit Length of Stay (number of days)

Time: Through study completion - up to 12 months

Description: Number of continuous calendar days or partial calendar days admitted to an acute care hospital.

Measure: Hospital Length of Stay (number of days)

Time: Through study completion - up to 12 months

HPO Nodes


HPO

Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


HPO Nodes


Reports

Data processed on December 13, 2020.

An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.

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