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| Name (Synonyms) | Correlation | |
|---|---|---|
| drug1215 | Dietary Intervention Wiki | 0.27 |
| drug4811 | washed microbiota transplantation Wiki | 0.27 |
| drug872 | Centrum Adult (under 50) multivitamin Wiki | 0.27 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| drug3371 | Ringer solution Wiki | 0.27 |
| drug4148 | Unfractionated heparin nebulized Wiki | 0.27 |
| drug1128 | DAS181 COVID-19 Wiki | 0.27 |
| drug3114 | Prophylactic/Intermediate Dose Enoxaparin Wiki | 0.27 |
| drug2163 | Lopinavir and Ritonavir Tablets Wiki | 0.27 |
| drug4794 | unfractionated heparin Wiki | 0.27 |
| drug331 | Apixaban Wiki | 0.27 |
| drug1129 | DAS181 OL Wiki | 0.27 |
| drug4355 | acetylsalicylic acid Wiki | 0.27 |
| drug2051 | JNJ-53718678 Wiki | 0.27 |
| drug3802 | Sulfonatoporphyrin(TPPS) plus Sunlight exposure. Wiki | 0.27 |
| drug1717 | Heparin sodium Wiki | 0.27 |
| drug4021 | Tissue plasminogen activator Wiki | 0.27 |
| drug852 | Cardiac surgery Wiki | 0.27 |
| drug3079 | PreserVision AREDS formulation gel tabs Wiki | 0.27 |
| drug4793 | unfractionated Heparin Wiki | 0.19 |
| drug343 | Arbidol Wiki | 0.19 |
| drug1398 | Enoxaparin 40 Mg/0.4 mL Injectable Solution Wiki | 0.19 |
| drug3651 | SnPP Protoporphyrin plus Sunlight exposure Wiki | 0.15 |
| drug4650 | placebo Wiki | 0.14 |
| drug1127 | DAS181 Wiki | 0.11 |
| drug2365 | Methylprednisolone Wiki | 0.07 |
| drug1047 | Convalescent Plasma Wiki | 0.05 |
| drug2916 | Placebo Wiki | 0.03 |
| drug1775 | Hydroxychloroquine Wiki | 0.03 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| D018184 | Paramyxoviridae Infections NIH | 0.15 |
| D020141 | Hemostatic Disorders NIH | 0.14 |
| D001778 | Blood Coagulation Disorders NIH | 0.14 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| D011655 | Pulmonary Embolism NIH | 0.13 |
| D004617 | Embolism NIH | 0.13 |
| D003141 | Communicable Diseases NIH | 0.12 |
| D013927 | Thrombosis NIH | 0.11 |
| D054556 | Venous Thromboembolism NIH | 0.09 |
| D018357 | Respiratory Syncytial Virus Infections NIH | 0.09 |
| D020246 | Venous Thrombosis NIH | 0.08 |
| D007239 | Infection NIH | 0.08 |
| D006331 | Heart Diseases NIH | 0.07 |
| D013923 | Thromboembolism NIH | 0.06 |
| D011024 | Pneumonia, Viral NIH | 0.06 |
| D011014 | Pneumonia NIH | 0.06 |
| D002318 | Cardiovascular Diseases NIH | 0.05 |
| D012141 | Respiratory Tract Infections NIH | 0.04 |
| D045169 | Severe Acute Respiratory Syndrome NIH | 0.03 |
| D016638 | Critical Illness NIH | 0.03 |
| D018352 | Coronavirus Infections NIH | 0.03 |
| D014777 | Virus Diseases NIH | 0.03 |
| D013577 | Syndrome NIH | 0.02 |
| D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.02 |
| D055371 | Acute Lung Injury NIH | 0.02 |
| D012128 | Respiratory Distress Syndrome, Adult NIH | 0.02 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0001928 | Abnormality of coagulation HPO | 0.14 |
| HP:0002204 | Pulmonary embolism HPO | 0.13 |
| HP:0002625 | Deep venous thrombosis HPO | 0.08 |
| Name (Synonyms) | Correlation | |
|---|---|---|
| HP:0001907 | Thromboembolism HPO | 0.06 |
| HP:0002090 | Pneumonia HPO | 0.06 |
| HP:0001626 | Abnormality of the cardiovascular system HPO | 0.05 |
| HP:0011947 | Respiratory tract infection HPO | 0.04 |
Navigate: Correlations HPO
There are 14 clinical trials
The ongoing COVID-19 pandemic affects millions of humans worldwide and has led to thousands of acute medical hospitalizations. There is evidence that hospitalized cases often suffer from an important infection-related coagulopathy and from elevated risks of thrombosis. Anticoagulants may have positive effects here, to reduce the burden of thrombotic disease and the hyperactivity of coagulation, and may also hold beneficial anti-inflammatory effects against sepsis and the development of ARDS. The investigators hypothesize that high-dose anticoagulants, compared with low-dose anticoagulants, lower the risk of venous and arterial thrombosis, disseminated intravascular coagulation (DIC) and mortality. This open-label controlled trial will randomize hospitalized adults with severe COVID-19 infection to therapeutic anticoagulation vs. thromboprophylaxis during the hospital stay.
Description: Risk of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality
Measure: Composite outcome of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality Time: 30 daysDescription: Risk of ischemic stroke, myocardial infarction and/or limb ischemia
Measure: Arterial thrombosis Time: 30 daysDescription: Risk of symptomatic venous thromboembolism or asymptomatic proximal leg deep vein thrombosis
Measure: Venous thromboembolism Time: 30 daysDescription: Risk of DIC
Measure: Disseminated intravascular coagulation Time: 30 daysDescription: Risk of all-cause mortality
Measure: All-cause mortality Time: 30 daysDescription: Risk of SIC
Measure: Sepsis-induced coagulopathy Time: 30 daysDescription: Risk of ARDS
Measure: Acute respiratory distress syndrome Time: 30 daysDescription: Number of days with these care processes
Measure: Durations of hospital stay, ICU stay, ventilation Time: 30 daysDescription: Highest score per participant
Measure: Sequential organ failure assessment score Time: 30 daysDescription: Risk of clinical deterioration
Measure: Clinical deterioration Time: 30 daysDescription: Risk of ISTH-defined major bleeding
Measure: Major bleeding Time: 30 daysDescription: Risk of ISTH-defined CRNMB
Measure: Clinically relevant non-major bleeding Time: 30 daysDescription: Risk of documented HIT
Measure: Heparin-induced thrombocytopenia Time: 30 daysThe purpose of this study is to determine whether a higher dose of low molecular weight heparin (enoxaparin 40 mg b.i.d.) is superior than the standard prophylaxis dose (enoxaparin 40 mg o.d.) in reducing thromboembolic events in COVID-19 patients.
Description: Deep vein thrombosis events diagnosed by serial compression ultrasonography and pulmonary embolism events diagnosed by computed tomography scan
Measure: Incidence of venous thromboembolism detected by imaging Time: 30 daysDescription: death, venous thromboembolism, use of mechanical ventilation, stroke, acute myocardial infarction and admission to an intensive care
Measure: In hospital major complications Time: 30 daysDescription: Deep venous thrombosis events diagnosed by serial compression ultrasonography
Measure: Number of deep venous thrombosis events Time: 30 daysDescription: Maximum sequential organ failure assessment (SOFA) score comparison between the two groups. The SOFA score ranges from 0 to 24. Higher SOFA score is associated with a greater risk of death or prolonged intensive care unit stay.
Measure: Sequential organ failure assessment Time: 30 daysDescription: To compare C-reactive protein levels as % above the upper reference limit [URL]) among the two groups.
Measure: C-reactive protein Time: 30 daysDescription: To compare Interleukin-6 levels as % above the upper reference limit [URL]) among the two groups.
Measure: Interleukin-6 Time: 30 daysDescription: To D-dimer compare levels as % above the upper reference limit [URL]) among the two groups.
Measure: D-dimer Time: 30 daysDescription: To compare hs-troponin levels as % above the upper reference limit [URL]) among the two groups.
Measure: hs-troponin levels Time: 30 daysDescription: To compare the incidence of SARS-CoV-2-related Acute Respiratory Distress Syndrome (ARDS) between the two groups.
Measure: Acute Respiratory Distress Syndrome Time: 30 daysDescription: To compare length of hospital stay between the two groups.
Measure: Hospital stay Time: 30 daysDescription: To compare measures of right ventricular function at trans-thoracic echocardiography or CT between admission and follow-up, whenever available
Measure: Right ventricular function Time: 30 daysDescription: Pulmonary embolism events diagnosed by computed tomography scan
Measure: Number of pulmonary embolism events Time: 30 daysWorldwide observational studies indicate a significant prothrombogenic effect associated with SARS-CoV-2 infection with a high incidence of venous thromboembolism (VTE), notably life-threatening pulmonary embolism. According to recommendations for acute medical illnesses, all COVID-19 hospitalized patients should be given VTE prophylaxis such as a low molecular weight heparin (LMWH). A standard prophylactic dose (eg. Enoxaparin 4000IU once daily) could be insufficient in obese patients and VTE has been reported in patients treated with a standard prophylactic dose. In COVID-19 patients, guidelines from several international societies confirm the existence of an hypercoagulability and the importance of thromboprophylaxis but the "optimal dose is unknown" and comparative studies are needed. In view of these elements, carrying out a trial comparing various therapeutic strategies for the prevention of VTE in hospitalized patients with COVID-19 constitutes a health emergency. Thus, we hypothesize that an increased prophylactic dose of weight-adjusted LMWH would be greater than a lower prophylactic dose of LMWH to reduce the risk of life-threatening VTE in hospitalized patients. The benefit-risk balance of this increase dose will be carefully evaluated because of bleeding complications favored by possible renal / hepatic dysfunctions, drug interactions or invasive procedures in COVID-19 patients. This multicenter randomized (1:1) open-label controlled trial will randomize hospitalized adults with COVID-19 infection to weight-adjusted prophylactic dose vs. lower prophylactic dose of LMWH.
Description: Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death
Measure: Venous thromboembolism Time: 28 daysDescription: Risk of major bleeding defined by the ISTH
Measure: Major bleeding Time: 28 daysDescription: Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH
Measure: Major Bleeding and Clinically Relevant Non-Major Bleeding Time: 28 daysDescription: Risk of Venous Thromboembolism and Major Bleeding
Measure: Net Clinical Benefit Time: 28 days and 2 monthsDescription: Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb
Measure: Venous Thromboembolism at other sites Time: 28 daysDescription: Risk of arterial thrombosis at any sites
Measure: Arterial Thrombosis Time: 28 daysDescription: Risk of all-cause mortality
Measure: All-Cause Mortality Time: 28 days and 2 monthsDescription: Identification of associations between the risk of venous thromboembolism and clinical (eg. past medical history of thrombosis, cardiovascular risk factors, treatments, severity of COVID-19) and laboratory variables (e.g. D-dimers, fibrinogen, CRP) collected in the eCRF
Measure: Factors associated with the risk of venous thromboembolism Time: 28 daysWorldwide observational studies indicate a significant prothrombogenic effect associated with SARS-CoV-2 infection with a high incidence of venous thromboembolism (VTE), notably life-threatening pulmonary embolism. According to recommendations for acute medical illnesses, all COVID-19 hospitalized patients should be given VTE prophylaxis such as a low molecular weight heparin (LMWH). A standard prophylactic dose (eg. Enoxaparin 4000IU once daily) could be insufficient in obese patients and VTE has been reported in patients treated with a standard prophylactic dose. In COVID-19 patients, guidelines from several international societies confirm the existence of an hypercoagulability and the importance of thromboprophylaxis but the "optimal dose is unknown" and comparative studies are needed. In view of these elements, carrying out a trial comparing various therapeutic strategies for the prevention of VTE in hospitalized patients with COVID-19 constitutes a health emergency. Thus, we hypothesize that an increased prophylactic dose of weight-adjusted LMWH would be greater than a lower prophylactic dose of LMWH to reduce the risk of life-threatening VTE in hospitalized patients. The benefit-risk balance of this increase dose will be carefully evaluated because of bleeding complications favored by possible renal / hepatic dysfunctions, drug interactions or invasive procedures in COVID-19 patients. This multicenter randomized (1:1) open-label controlled trial will randomize hospitalized adults with COVID-19 infection to weight-adjusted prophylactic dose vs. lower prophylactic dose of LMWH.
Description: Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death
Measure: Venous thromboembolism Time: 28 daysDescription: Risk of major bleeding defined by the ISTH
Measure: Major bleeding Time: 28 daysDescription: Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH
Measure: Major Bleeding and Clinically Relevant Non-Major Bleeding Time: 28 daysDescription: Risk of Venous Thromboembolism and Major Bleeding
Measure: Net Clinical Benefit Time: 28 days and 2 monthsDescription: Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb
Measure: Venous Thromboembolism at other sites Time: 28 daysDescription: Risk of arterial thrombosis at any sites
Measure: Arterial Thrombosis Time: 28 daysDescription: Risk of all-cause mortality
Measure: All-Cause Mortality Time: 28 days and 2 monthsDescription: Identification of associations between the risk of venous thromboembolism and clinical (eg. past medical history of thrombosis, cardiovascular risk factors, treatments, severity of COVID-19) and laboratory variables (e.g. D-dimers, fibrinogen, CRP) collected in the eCRF
Measure: Factors associated with the risk of venous thromboembolism Time: 28 daysThe coronavirus disease 2019 (COVID-19) global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality in over 170 countries. Increasing age and burden of cardiovascular comorbidities are associated with a worse prognosis among patients with COVID-19. In addition, serologic markers of more severe disease including coagulation abnormalities and thrombocytopenia, are not uncommon among patients hospitalized with severe COVID-19 infection and are more common in patients who died in-hospital. As the COVID-19 pandemic continues to grow, there is a pressing need to identify safe, effective, and widely available therapies that can be scaled and rapidly incorporated into clinical practice. Understanding the putative mechanism of increased mortality risk associated with abnormal coagulation function and cardiac injury is critical to guide studies of promising therapeutic interventions. Published and anecdotal reports indicate that endothelial dysfunction and thrombosis are common in critically ill patients with COVID-19, including reports of diffuse microvascular thrombosis in the lungs, heart, liver, and kidneys. Patients with cardiovascular disease (CVD) and CVD risk factors are known to have endothelial dysfunction and a heightened risk of thrombosis. A recent study of COVID-19 inpatients from Wuhan, China observed that an elevated D-dimer level greater than 1 ug/mL was associated with an 18 times higher risk of in-hospital death, underscoring the importance of increased coagulation activity as a potential modifiable risk marker that may drive end-organ injury. Given the established link between endothelial dysfunction and thrombosis in patients with cardiovascular disease, and the association between coagulopathy and adverse outcomes in patients with sepsis, the association between increased coagulation activity, end-organ injury, and mortality risk may represent a modifiable risk factor among COVID-19 patients with critical illness. Therefore, we propose to conduct a randomized, open-label trial of therapeutic anticoagulation in COVID-19 patients with an elevated D-dimer to evaluate the efficacy and safety.
Description: Aim 1 - Risk of death, cardiac arrest, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, or hemodynamic shock.
Measure: Number of patients with the composite efficacy endpoint of death, cardiac arrest, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, or hemodynamic shock. Time: 12 weeksDescription: Aim 2 - Risk of major bleeding event according to the International Society on Thrombosis and Haemostasis (ISTH) definition.
Measure: Number of patients with a major bleeding event according to the International Society on Thrombosis and Haemostasis (ISTH) definition. Time: 12 weeksThe aim of this study is to test the hypothesis that prophylaxis of severe COVID-19 patients with treatment dose LMWH leads to better thromboembolic-free outcomes and associated complications during hospitalization than prophylaxis with institutional standard of care with prophylactic to intermediate-doses of UFH or LMWH
Description: Risk of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Day 30 ± 2 days.
Measure: Composite outcome of arterial thromboembolic events, venous thromboembolic events and all-cause mortality at Day 30 ± 2 days. Time: Day 30 ± 2 daysDescription: Risk of major bleeding defined using the International Society of Thrombosis and Haemostasis (ISTH) criteria
Measure: Major bleeding Time: Day 30 ± 2 daysDescription: The composite of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Hospital Day 10 + 4
Measure: Composite outcome of arterial thromboembolic events, venous thromboembolic events and all-cause mortality at Hospital Day 10 + 4 Time: Day 10 + 4Description: Sepsis-induced coagulopathy (SIC) score based on ISTH guidelines. Platelets, K/uL (thousands per microliter) [0-2] INR (International Normalized Ratio) [0-2] D-Dimer Levels, ng/mL [0-3] Fibrinogen, mg/dL [0-1] Calculated (SIC) scores greater or equal to 4 predicted higher mortality rates within 30 days and greater risk of pulmonary embolism.
Measure: Sepsis-induced coagulopathy (SIC) score Time: Day 30 ± 2 days.Description: Progression to Acute Respiratory Distress Syndrome (ARDS) based on monitoring of patient conditions.
Measure: Progression to Acute Respiratory Distress Syndrome (ARDS) Time: Day 30 ± 2 days.Description: Need for Intubation will be based on monitoring of patient conditions.
Measure: Need for Intubation Time: Day 30 ± 2 days.Description: Need for Re-hospitalization will be based on monitoring of patient conditions.
Measure: Re-hospitalization Time: Day 30 ± 2 days.Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation. Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are: 1. More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay: 1. Death 2. Acute Myocardial Infarction [AMI] 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] 4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation 5. Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation 2. Similar in terms of major bleeding risk during hospital stay
Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation
Measure: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: Time: through study completion, up to 30 daysDescription: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation Improvement of laboratory parameters of disease severity, including: D-dimer level Plasma fibrinogen levels Mean Platelet Volume Lymphocyte/Neutrophil ratio IL-6 plasma levels
Measure: Any of the following events occurring within the hospital stay Time: through study completion, up to 30 daysDescription: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.
Measure: Mortality at 30 days Time: 30 daysGeneral objective of the study To assess the efficacy and safety of enoxaparin in hospitalized patients with moderate to severe COVID-19 (Coronavirus Disease 2019) infection. Study Design The study consists of two parts: - a phase II single-arm interventional prospective study including all patients treated with the study drug; - an observational prospective cohort study including all patients screened for receiving the study drug but not included in the phase II study. Patients will be enrolled from "date of study approval" for 1 month. Each patient will be followed-up for a minimum of 90 days after COVID19 diagnosis.
Description: Rates of hospitalized patients dead for all-cause within 30 days and 90 days from the first LMWH subcutaneous injection
Measure: To investigate the efficacy of enoxaparin in improving the clinical outcome of hospitalized patients with moderate-severe COVID-19. Time: 30 days and 90 days from the first LMWH subcutaneous injectionDescription: Based on the four levels scale of severity of symptoms. Any change from one level to another will be detected for all the enrolled patients, in order to evalutate the clinical efficacy of enoxaparin on the outcome of COVID 19.
Measure: To investigate the efficacy of enoxaparin in improving the clinical outcome of hospitalized patients with moderate-severe COVID-19. Time: This evaluation will be performed at 30 days and 90 days from the first LMWH subcutaneous injectionDescription: Evolution of the clinical severity during treatment, based on the number and rate of patients admitted to ICU and the length of their ICU stay
Measure: To investigate the efficacy of enoxaparin in improving the clinical outcome of hospitalized patients with moderate-severe COVID-19. Time: This evaluation will be performed at 14 days (the last day of treatment adminstration), at 30 days and 90 days from the first LMWH subcutaneous injectionDescription: Difference between groups in number of days of hospitalization from admission to discharge
Measure: To investigate the efficacy of enoxaparin in improving the clinical outcome of hospitalized patients with moderate-severe COVID-19. Time: This evaluation will be performed at 90 days from admissionDescription: Rate of adverse events (AEs) during treatment, at the end of treatment (EOT) and at 30 days after EOT. • Severity of AEs classified according to common terminology criteria for adverse events (CTCAE). The worst degree ever suffered will be considered.
Measure: To analyse the safety of enoxaparin in hospitalized patients with moderatesevere COVID-19. Time: 45 daysDescription: Occurrence of thromboembolic event at 90 days after COVID-19 diagnosis. Description of the type, distribution and severity of thromboembolic events.
Measure: To describe the rates and the types of thromboembolic events among hospitalized patients with confirmed diagnosis of COVID-19. Time: 90 daysHypercoagulability has been demonstrated in COVID-19, leading to respiratory distress and increased mortality. This is adaptive clinical trial to compare effectiveness and safety of four therapeutic strategies in hospital mortality in patients with COVID-19: standard prophylaxis, therapeutic dose anticoagulation, inhaled UFH associated with standard prophylaxis and ASA associated with standard prophylaxis.
Description: Number of COVID-19 positive patients who are alive within 30 days of symptoms onset
Measure: Hospital discharge - alive / death Time: 30 daysDescription: Comparison of length of mechanical ventilation free days between each treatment arm
Measure: Length of mechanical ventilation free days Time: 30 daysDescription: Comparison of length of renal replacement therapy free days between each treatment arm
Measure: Length of renal replacement therapy free days Time: 30 daysDescription: Comparison of number of thrombosis events between each treatment arm.
Measure: Number of documented venous thromboembolism or arterial thrombosis Time: 3 monthsEvidence has shown that COVID-19 infections can lead to an increased risk of blood clots. These blood clots can lead to individuals being admitted to hospital, or, unfortunately in severe cases, death. Enoxaparin is a blood-thinning drug which has been used by doctors and nurses in hospitals for many years to prevent the thickening of blood which may lead to a clot. It is easier for doctors to prevent new blood clots from forming than treating existing blood clots. Currently, there are no treatments for COVID-19. There is an urgent need to find a safe and effective treatment to prevent worsening of the disease that may lead to hospital admission and/or death. The ETHIC (Early Thromboprophylaxis in COVID-19) study aims to find out if giving enoxaparin in an early stage of the COVID-19 disease can prevent individuals being admitted to hospital and/or death. The study will take place in approximately 8 to 10 countries, in approximately 30 to 50 centres. Patients will be allowed to take part if they have had a confirmed COVID-19 infection, are ≥ 55 years of age and have at least two of the following additional risk factors; age ≥ 70 years, body mass index > 25 kg/m2, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, or corticosteroid use. Half the patients in the study will receive the blood-thinning drug enoxaparin for three weeks, and half will receive no treatment. Individuals will be randomly allocated to one of these groups. After 21 days, the number of patients in each group who were either admitted to hospital, or died, will be compared. The number of patients in each group who developed a blood clot (venous thromboembolism) will also be compared. Further comparisons will be made at both 50 and 90 days after the beginning of the study.
Description: Hospital admission including: Pneumonia Acute Respiratory distress syndrome Admission to intensive care unit (ICU) Mechanical ventilation (MV)/intubation requirement Continuous positive airway pressure (CPAP)/Non-invasive ventilation Extracorporeal membrane oxygenation (ECMO)
Measure: Hospital Admission Time: 21 daysDescription: Hospital admission including: Pneumonia Acute Respiratory distress syndrome Admission to intensive care unit (ICU) Mechanical ventilation (MV)/intubation requirement Continuous positive airway pressure (CPAP)/Non-invasive ventilation Extracorporeal membrane oxygenation (ECMO)
Measure: Hospital Admission Time: 50 daysDescription: Hospital admission including: Pneumonia Acute Respiratory distress syndrome Admission to intensive care unit (ICU) Mechanical ventilation (MV)/intubation requirement Continuous positive airway pressure (CPAP)/Non-invasive ventilation Extracorporeal membrane oxygenation (ECMO)
Measure: Hospital Admission Time: 90 daysDescription: All-cause Cardiovascular Non-Cardiovascular Specific causes Fatal bleed
Measure: Death Time: 21 daysDescription: All-cause Cardiovascular Non-Cardiovascular Specific causes Fatal bleed
Measure: Death Time: 50 daysDescription: All-cause Cardiovascular Non-Cardiovascular Specific causes Fatal bleed
Measure: Death Time: 90 daysDescription: Frequency Location Treatment (transfusion and units of blood products transfused) Severity (classified as major, clinically relevant non-major and minor)
Measure: Bleeding (as defined by ISTH criteria) Time: 21 and 50 daysDescription: Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
Measure: Diagnosis of VTE Time: 21, 50 and 90 daysViral infections provoke the systemic inflammatory response and cause an imbalance between the procoagulant and anticoagulant homeostatic mechanisms. Multiple pathogenic mechanisms are involved, including endothelial dysfunction, increased von Willebrand factor, Toll receptor activation, and tissue factor pathway activation. D-dimer levels greater than 1000 ng / mL are associated with an 18-fold increased risk of mortality. In this context, many patients may require prophylaxis or antithrombotic treatment with low molecular weight heparins. Currently, there is no validated scheme on the dose and timing of the use of antithrombotic drugs. The study aims to identify the effect of two anticoagulant strategies (prophylactic and therapeutic) on the progression to ventilatory support or death in patients with COVID-19 infection who require hospital care.
Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) on ventilatory support time in patients requiring hospital care for COVID-19 infection.
Measure: low molecular weight heparin (enoxaparin) and ventilatory support time Time: 30 daysDescription: To compare oral anticoagulation therapy by administering Rivaroxaban 10mg PO every 24 hours on early thrombotic complications
Measure: thrombotic complications and Rivaroxaban Time: 30 daysDescription: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) on the length of hospital stay in patients requiring hospital care for COVID-19 infection.
Measure: low molecular weight heparin (enoxaparin) and length of hospital stay Time: 30 daysDescription: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) over mortality rate in patients requiring hospital care for COVID-19 infection.
Measure: low molecular weight heparin (enoxaparin) and mortality rate Time: 30 daysCoronavirus Disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to unprecedented morbidity and mortality in the modern era. To date, nearly 13 million people have contracted COVID-19, leading to more than 550,000 deaths worldwide. As the number of affected individuals continues to climb, effective strategies for treatment and prevention of the disease are of paramount importance. SARS-CoV-2 is understood to directly invade cells via the human angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed predominantly in the lungs but also throughout the cardiovascular system. Thus, while acute respiratory distress syndrome remains a feared complication, new thromboembolic disease has emerged as a common and potentially catastrophic manifestation of COVID-19.
Description: The time to first event rate within 30 days of randomization of the composite of all-cause mortality, intubation requiring mechanical ventilation, systemic thromboembolism (including pulmonary emboli) confirmed by imaging or requiring surgical intervention OR ischemic stroke confirmed by imaging.
Measure: Time to first event Time: 30 daysDescription: Number of in-hospital rate of BARC 3 or 5 bleeding (binary). BARC Type 3: a. Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding b. Overt bleeding plus hemoglobin drop < 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision. BARC Type 5: Probable fatal bleeding Definite fatal bleeding (overt or autopsy or imaging confirmation)
Measure: Number of in-hospital rate of BARC 3 or 5 Time: 30 daysDescription: Myocardial infarction (according to the 4th universal definition, types 1,2, and 3)
Measure: Number of participants with Myocardial infarction Time: 30 days after randomizationDescription: Myocardial infarction (according to the 4th universal definition, types 1,2, and 3)
Measure: Number of participants with Myocardial infarction Time: 90 days after randomizationDescription: Deep vein thrombosis with confirmation on imaging
Measure: Number of participants with Deep Vein Thrombosis Time: 30 days after randomizationDescription: Deep vein thrombosis with confirmation on imaging
Measure: Number of participants with Deep Vein Thrombosis Time: 90 days after randomizationDescription: Intubation and mechanical ventilation
Measure: Number of participants requiring Ventilation Time: 30 after randomizationDescription: Intubation and mechanical ventilation
Measure: Number of participants requiring Ventilation Time: 90 days after randomizationDescription: All-cause death
Measure: Number of All Death Time: 30 days after randomizationDescription: All-cause death
Measure: Number of All Death Time: 90 days after randomizationDescription: Cause of Death
Measure: Cause of Death Time: 30 days after randomizationDescription: Cause of Death
Measure: Cause of Death Time: 90 days after randomizationDescription: Stroke confirmed by imaging or autopsy (all, ischemic and hemorrhagic)
Measure: Number of participants with Stroke Time: 30 days after randomizationDescription: Stroke confirmed by imaging or autopsy (all, ischemic and hemorrhagic)
Measure: Number of participants with Stroke Time: 90 days after randomizationDescription: Pulmonary emboli confirmed by imaging or autopsy
Measure: Number of participants with Pulmonary Emboli Time: 30 days after randomizationDescription: Pulmonary emboli confirmed by imaging or autopsy
Measure: Number of participants with Pulmonary Emboli Time: 90 days after randomizationDescription: Systemic thromboembolism confirmed by imaging or requiring surgical intervention
Measure: Number of participants with Systemic Thromboembolism Time: 30 days after randomizationDescription: Systemic thromboembolism confirmed by imaging or requiring surgical intervention
Measure: Number of participants with Systemic Thromboembolism Time: 90 days after randomizationSARS-CoV-2 infection seems to induce in most critical cases an excessive and aberrant hyper-inflammatory host immune response that is associated with a so-called "cytokine storm", moreover pro-thrombotic derangements of haemostatic system is another common finding in most severe forms of COVID19 infections, which may be explained by the activation of coagulative cascade primed by inflammatory stimuli, in line with what is observed in many other forms of sepsis. Targeting inflammatory responses exploiting steroids' anti-inflammatory activity along with thrombosis prevention may be a promising therapeutic option to improve patients' outcome. Despite the biological plausibility, no good evidence is available on the efficacy and safety of heparin on sepsis patients, and many issues have to be addressed, regarding the proper timing, dosages and administration schedules of anticoagulant drugs. The primary objective is to assess the hypothesis that an adjunctive therapy with steroids and unfractionated heparin (UFH) or with steroids and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill patients with pneumonia from COVID- 19 infection compared to low molecular weight heparin (LMWH) alone. Mortality will be measured at 28 days. The study is designed as a multicenter, national, interventional, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned in a ratio 1:1:1 to one of the three treatment groups: LMWH group, LMWH+steroids or UFH+steroid group. A possible result showing the efficacy of the composite treatment in reducing the mortality rate among critically ill patients with pneumonia from COVID-19 infection will lead to a revision of the current clinical approach to this disease.
Description: All-cause mortality at day 28, defined as the comparison of proportions of patients death for any cause at day 28 from randomization.
Measure: All-cause mortality at day 28 Time: Day 28 from randomizationDescription: All-cause mortality at ICU discharge, defined as the comparison of proportions of patients death for any cause at ICU discharge.
Measure: All-cause mortality at ICU discharge Time: from randomization to ICU discharge, censored at day 30Description: All-cause mortality at Hospital discharge, defined as the comparison of proportions of patients death for any cause at hospital discharge
Measure: All-cause mortality at hospital discharge Time: from randomization to ICU discharge, censored at day 90Description: Occurrence of rescue administration of high-dose steroids or immune-modulatory drugs
Measure: Need of rescue administration of high-dose steroids or immune-modulatory drugs Time: from randomization to ICU discharge, censored at day 28Description: Occurrence of new organ dysfunction during ICU stay. Organ dysfunction is defined as a Sequential Organ Failure Assessment (SOFA) score ≥3 for the corresponding organ occurring after randomization.
Measure: New organ dysfunction during ICU stay Time: From randomization to ICU discharge, censored at day 28Description: Grade of organ dysfunction during ICU stay, grade of dysfunction is measured with Sequential Organ Failure Assessment (SOFA) score daily from randomization to day 28 or ICU discharge.
Measure: Grade of organ dysfunction during ICU stay Time: From randomization to ICU discharge, censored at day 28Description: Total number of days between ICU discharge and day 28. If death occurs during the ICU stay before day 28 the ICU free days calculation will be 0. The ICU readmission before day 28 after randomization will be considered.
Measure: ICU free days at day 28 Time: From randomization to day 28Description: Occurrence of new infections including bacterial infections, fungal infections by Candida, Aspergillus, and viral reactivations including Adenovirus, Herpes Virus e Cytomegalovirus
Measure: Occurrence of new infections Time: from randomization to day 28Description: Total number of days that patient is alive and free of ventilation between randomisation and day 28. Ventilation is considered as positive pressure ventilation, either invasive or non-invasive. Periods of assisted breathing lasting less than 24 hours for surgical procedures will not count against the ventilation free days calculation.
Measure: Ventilation free days at day 28 Time: From randomization to day 28, censored at hospital dischargeDescription: Total number of days that patient is alive and free of vasopressors between randomisation and day 28.
Measure: Vasopressors free-days at day 28 Time: From randomization to day 28, censored at hospital dischargeDescription: Occurrence of switch from non-invasive to invasive mechanical ventilation
Measure: Switch from non-invasive to invasive mechanical ventilation Time: from randomization to ICU discharge, censored at day 28Description: Total number of hours from start of non-invasive to invasive ventilation to switch to invasive ventilation
Measure: Delay from start of non-invasive ventilation to switch to invasive ventilation Time: from randomization to ICU discharge, censored at day 28Description: Adverse events occurred from randomization to day 28. Events that are part of the natural history of the primary disease process or expected complications of critical illness will not be reported as adverse events.
Measure: Occurrence of protocol related adverse events Time: From randomization to day 28Description: Occurrence of objectively confirmed venous thromboembolism, stroke or myocardial infarction
Measure: Occurrence of venous thromboembolism, stroke or myocardial infarction Time: from randomization to ICU discharge, censored at day 28Description: Occurrence of major bleeding defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death)
Measure: Occurrence of major bleeding (safety end point) Time: from randomization to ICU discharge, censored at day 28Description: Occurrence of clinically relevant non-major bleeding defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, or 100 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug.
Measure: Occurrence of clinically relevant non-major bleeding (safety end point) Time: from randomization to ICU discharge, censored at day 28Description: Mean arterial pressure will be measured in millimeters of mercury
Measure: Mean arterial pressure Time: Daily from inclusion until ICU discharge, censored day 28Description: hearth rate will be measured in beats per minute
Measure: hearth rate Time: Daily from inclusion until ICU discharge, censored day 28Description: respiratory rate will be measured in breaths per minute
Measure: respiratory rate Time: Daily from inclusion until ICU discharge, censored day 28Description: diuresis will be measured daily in milliliters of urine output in the previous 24 hours
Measure: diuresis Time: Daily from inclusion until ICU discharge, censored day 28Description: systemic body temperature will be measured in celsius degrees
Measure: systemic body temperature Time: Daily from inclusion until ICU discharge, censored day 28Description: fluid balance will be measured in milliliters of fluids input and output in the previous 24 hours
Measure: fluid balance Time: Daily from inclusion until ICU discharge, censored day 28Description: Haemoglobin will be measured in mg/dl
Measure: Haemoglobin concentration Time: Daily from inclusion to ICU discharge (censored at day 28)Description: platelets count will be measured in U 10^3/mm^3
Measure: platelets count Time: Daily from inclusion to ICU discharge (censored at day 28)Description: white blood cells count will be measured in U per 10^9/L
Measure: white blood cells count Time: Daily from inclusion to ICU discharge (censored at day 28)Description: troponin will be measured in µg/L
Measure: troponin Time: Daily from inclusion to ICU discharge (censored at day 28)Description: coagulative function will be measured with parameters INR, PT, aPTT
Measure: coagulative function Time: Daily from inclusion to ICU discharge (censored at day 28)Description: D-dimer will be measured in µg/ml
Measure: D-dimer Time: Daily from inclusion to ICU discharge (censored at day 28)Description: anti-thrombin will be measured as a percentage
Measure: anti-thrombin Time: Daily from inclusion to ICU discharge (censored at day 28)Description: liver function will be assessed through measurement of AST, ALT in U/L
Measure: Liver function Time: Daily from inclusion to ICU discharge (censored at day 28)Description: Bilirubin will be measured in mg/dL
Measure: Bilirubin Time: Daily from inclusion to ICU discharge (censored at day 28)Description: Creatinine will be measured in mg/dL
Measure: Creatinine Time: Daily from inclusion to ICU discharge (censored at day 28)Description: Blood cells count will be measured in Units per x 10^9/L of blood
Measure: Blood cells count Time: daily from inclusion to ICU discharge (censored at day 28)Description: C-reactive protein (CRP) will be measured in mg/dl
Measure: C-reactive protein (CRP) Time: daily from inclusion to ICU discharge (censored at day 28)Description: procalcitonin(PCT) wiull be measured in ng/ml
Measure: procalcitonin(PCT) Time: daily from inclusion to ICU discharge (censored at day 28)Description: interleukin 6 (IL-6) will be measured in pg/ml
Measure: interleukin 6 (IL-6) Time: daily from inclusion to ICU discharge (censored at day 28)Description: Ventilation mode will be cathegorized in spontaneous breathing, invasive or non invasive ventilation
Measure: Ventilation mode Time: Daily from inclusion to ICU discharge (censored at day 28)Description: inspired oxygen fraction will be measured in percentage of oxygen in inspired air
Measure: inspired oxygen fraction Time: Daily from inclusion to ICU discharge (censored at day 28)Description: Gas exchanges will be assessed by measurement of PaO2, PaCO2 in mmHg by arterial blood gas analysis
Measure: Gas exchanges Time: Daily from inclusion to ICU discharge (censored at day 28)Description: lactates will be measured in mMol/L
Measure: lactates Time: Daily from inclusion to ICU discharge (censored at day 28)Description: pH will be measured in pH scale
Measure: pH Time: Daily from inclusion to ICU discharge (censored at day 28)Description: oxygen saturation in blood will be measured in arterial and venous samples in percentage values
Measure: oxygen saturation in blood Time: Daily from inclusion to ICU discharge (censored at day 28)Description: New blood, respiratory and urinary-tract infections will be recorded
Measure: New infections Time: From randomization to day 28Description: Viral reactivation measured by CMV DNA titres will be recorded.
Measure: Viral reactivation Time: From randomization to day 28Description: Need of new renal replacement therapy (intermittent haemodialysis or continuous veno-venous hemofiltration) will be recorded.
Measure: Need of new renal replacement therapy Time: from randomization to day 28Description: Adjunctive treatment such as pronation cycles, Nitric Oxide or ECMO will be recorded
Measure: Adjunctive treatments Time: from randomization to ICU discharge (censored at day 28);To evaluate the safety and efficacy of the use of inhalational heparin in patients with pulmonary compromise / pneumonia / SARS associated with COVID-19, laboratory with marked inflammation parameters, and prothrombotic state secondary to it (Fibrinogen, Ferritin and / or elevated D-Dimer) , from admission to hospitalization. The combination of inhalation heparin combined with prophylactic doses of LMWH could reduce the progression to severe forms of the disease, and consequently the need for intensive care units and mechanical ventilation.
Description: Blood Gas criteria :PaO2 / FiO2 <200 (or the inability to maintain an SpO2 of at least 92% with a reservoir mask). Acute ventilatory failure (pH less than 7.35 with PaCO2 greater than 45 mmHg)
Measure: Percentage of patients requirement mechanical ventilation Time: 15 daysDescription: Mean every 48 hours PaO2 to FiO2 ratio
Measure: Percentage of patients with PaO2 to Fi02 ratio > 300 Time: 7 daysDescription: To compare the lengths of hospital-stay
Measure: Lengths of hospital-stay Time: Days 60Description: All cause mortality
Measure: Mortality rate Time: 30 daysAlphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on September 26, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
Drug Reports MeSH Reports HPO Reports