Name (Synonyms) | Correlation | |
---|---|---|
drug3037 | unfractionated Heparin Wiki | 0.33 |
drug2461 | Telephone interview Wiki | 0.33 |
drug581 | Clinical assessment Wiki | 0.33 |
drug942 | FilmArray Pneumonia Wiki | 0.33 |
drug596 | Cognitive Stimulation Wiki | 0.33 |
drug2727 | acetylsalicylic acid Wiki | 0.33 |
drug1925 | Prophylactic/Intermediate Dose Enoxaparin Wiki | 0.33 |
drug706 | DUR-928 Wiki | 0.33 |
drug2597 | Unfractionated heparin nebulized Wiki | 0.33 |
drug1199 | Information leaflet Wiki | 0.33 |
drug2673 | WALC-R Wiki | 0.33 |
drug854 | Enoxaparin 40 Mg/0.4 mL Injectable Solution Wiki | 0.24 |
drug2187 | Saliva collection Wiki | 0.15 |
drug1822 | Placebo Wiki | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
D060825 | Cognitive Dysfunction NIH | 0.35 |
D019965 | Neurocognitive Disorders NIH | 0.33 |
D003704 | Dementia NIH | 0.33 |
D060085 | Coinfection NIH | 0.24 |
D013927 | Thrombosis NIH | 0.15 |
D054556 | Venous Thromboembolism NIH | 0.13 |
D020246 | Venous Thrombosis NIH | 0.11 |
D011655 | Pulmonary Embolism NIH | 0.11 |
D020141 | Hemostatic Disorders NIH | 0.10 |
D004617 | Embolism NIH | 0.10 |
D001778 | Blood Coagulation Disorders NIH | 0.10 |
D013923 | Thromboembolism NIH | 0.09 |
D002318 | Cardiovascular Diseases NIH | 0.07 |
D011024 | Pneumonia, Viral NIH | 0.04 |
D011014 | Pneumonia NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0001268 | Mental deterioration HPO | 0.35 |
HP:0000726 | Dementia HPO | 0.33 |
HP:0002625 | Deep venous thrombosis HPO | 0.11 |
HP:0002204 | Pulmonary embolism HPO | 0.11 |
HP:0001928 | Abnormality of coagulation HPO | 0.10 |
HP:0001907 | Thromboembolism HPO | 0.08 |
HP:0001626 | Abnormality of the cardiovascular system HPO | 0.07 |
HP:0002090 | Pneumonia HPO | 0.02 |
There are 9 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 months