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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Corona Virus Infection; Hypercoagulability
• Intervention / Treatment: Drug: Enoxaparin; Drug: Enoxaparin; Drug: Rivaroxaban; Drug: Rivaroxaban; Drug: Apixaban; Drug: Apixaban

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• Egypt
  • Please Select
    • Cairo, Please Select, Egypt, 11314
      • Teachers Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The current research is including moderate and severe SARS-COV-2 patients receiving the same background treatment for 5 days, following an Institutional protocol for standard of care: hydroxychloroquine 400 mg daily, lopinavir/ritonavir 400/100 mg twice daily or/and remdisivir 200 mg LD then 100 once daily as a maintenance dose and anti-coagulation prophylaxis with enoxaparin subcutaneously once a day if D-dimmer between 500-1000 or enoxaparin therapeutic subcutaneously twice daily if D-dimmer >1000.

Description

Inclusion Criteria:

1. Age 18 to 65 years..
2. COVID-19 hospitalized patients with pneumonia proved by chest X-ray or CT scan.
3. Confirmed infection with COVID-19 virus using RT-PCR or strongly suspected to be infected with pending confirmation studies.
4. 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:

1. Age greater than 85 years-old
2. Creatinine clearance (CrCl)<10ml/min.
3. Severe circulatory shock with a dose of norepinephrine higher than 1.0 μg/kg/min.
4. Pregnant women.
5. Recent major surgery or severe trauma in the last 3 weeks or recent hemorrhagic stroke in the last 3 months.
6. Active bleeding, blood dyscrasia such as hemophilia and Von Willebrand factor deficiency.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Enoxaparin therapeutic dose	Drug: Enoxaparin; 0.5 mg/kg every 12 hours; Drug: Enoxaparin; 40 mg/day
Group 2; Enoxaparin prophylactic dose	Drug: Enoxaparin; 0.5 mg/kg every 12 hours; Drug: Enoxaparin; 40 mg/day
Group 3; Rivaroxaban therapeutic dose	Drug: Rivaroxaban; 10 mg once daily; Drug: Rivaroxaban; 20 mg once daily
Group 4; Rivaroxaban prophylactic dose	Drug: Rivaroxaban; 10 mg once daily; Drug: Rivaroxaban; 20 mg once daily
Group 5; Apixaban therapeutic dose	Drug: Apixaban; 2.5 mg twice daily; Drug: Apixaban; 5 mg twice daily
Group 6; Apixaban prophylactic dose	Drug: Apixaban; 2.5 mg twice daily; Drug: Apixaban; 5 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of hospitalization	Length of hospital stay	Two weeks
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

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

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: Misr International University

Publications and helpful links

General Publications

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2020
• Primary Completion (ACTUAL): October 1, 2021
• Study Completion (ACTUAL): December 1, 2021

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (ACTUAL): February 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Anticoagulants; Hypercoagulability
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Hematologic Diseases; COVID-19; Coronavirus Infections; Thrombophilia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Apixaban; Enoxaparin; Enoxaparin sodium
• Other Study ID Numbers: COVID-Anticoagulants

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No