Effect of Prophylactic and Therapeutic Anticoagulants in Egyptian Patients With COVID-19

Study Overview
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Brief Summary
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Since the end of 2019, Egypt and the whole world have been suffering from the Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization (WHO), since the emergence of this new pandemic, there have been more than 97 million confirmed cases of COVID-19 patients and two million death globally; around 160 thousand of these cases are in Egypt. Recent clinical investigations found a high incidence of thrombotic complications in these patients, even with the standard anticoagulant thromboprophylaxis.Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Among the pathological sequel of COVID-19 infection, is the presence of a micro-thrombi in the pulmonary circulation which was shown in several autopsy studies. This thrombosis is believed to contribute to gas exchange impairment among patients with COVID-19 infection. Some observational studies have shown anticoagulation benefits with reduced mortality, mainly in patients requiring mechanical ventilation. However, these findings remain uncertain and need to be validated in further studies. This study is performed to evaluate whether therapeutic anticoagulation could improve COVID-19 patients' clinical outcomes compared to prophylactic anticoagulation in terms of improving gas exchange, reducing the need to maintain mechanical ventilation, shortening hospital admission period and mortality rate as well as recovering D-dimmer levels to its normal values.

Official Title
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Effect of Prophylactic and Therapeutic Anticoagulants in Egyptian Patients With COVID-19

Conditions
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Covid19, Corona Virus Infection, Hypercoagulability

Intervention / Treatment
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* Drug: Enoxaparin
* Drug: Enoxaparin
* Drug: Rivaroxaban
* Drug: Rivaroxaban
* Drug: Apixaban
* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 65 years.. COVID-19 hospitalized patients with pneumonia proved by chest X-ray or CT scan. Confirmed infection with COVID-19 virus using RT-PCR or strongly suspected to be infected with pending confirmation studies. Prothrombin time/international normalized ratio (INR)<1.5; activated partial thromboplastin time (aPTT)/ratio<1.5, and platelet count greater than 100,000/mm3. Exclusion Criteria: Age greater than 85 years-old Creatinine clearance (CrCl)<10ml/min. Severe circulatory shock with a dose of norepinephrine higher than 1.0 μg/kg/min. Pregnant women. Recent major surgery or severe trauma in the last 3 weeks or recent hemorrhagic stroke in the last 3 months. Active bleeding, blood dyscrasia such as hemophilia and Von Willebrand factor deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Enoxaparin therapeutic dose | Drug: Enoxaparin<br>* 40 mg/day<br>|
| Group 2<br>Enoxaparin prophylactic dose | Drug: Enoxaparin<br>* 0.5 mg/kg every 12 hours<br>|
| Group 3<br>Rivaroxaban therapeutic dose | Drug: Rivaroxaban<br>* 20 mg once daily<br>|
| Group 4<br>Rivaroxaban prophylactic dose | Drug: Rivaroxaban<br>* 10 mg once daily<br>|
| Group 5<br>Apixaban therapeutic dose | Drug: Apixaban<br>* 5 mg twice daily<br>|
| Group 6<br>Apixaban prophylactic dose | Drug: Apixaban<br>* 2.5 mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clotting factors level | Difference in clotting factors levels between baseline during inclusion in the study and before discharge. | Two weeks | 
| Change in gas exchange over time | Difference between ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, and before discharge. | Two weeks | 
| Time to increase in oxygenation | Time to increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2 | Two weeks | 
| Duration of hospitalization | Length of hospital stay | Two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitoring of adverse events | Any signs or symptoms of bleeding will be monitored daily | Two weeks | 
| In hospital mortality rate | Death occurrence during hospitalization | Two weeks | 
| Monitoring of hemoglobin levels. | Difference in hemoglobin levels between baseline during inclusion in the study and before discharge. | Two weeks | 
| Monitoring of platelets levels | Difference in platelets levels between baseline during inclusion in the study and before discharge | Two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Hypercoagulability, Anticoagulants