Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care (ECRU)
Primary Purpose
COVID-19
Status
Not yet recruiting
Phase
Phase 2
Locations
Pakistan
Study Type
Interventional
Intervention
Apixaban
Rivaroxaban
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Anticoagulation, Apixaban
Eligibility Criteria
Inclusion Criteria:
- Adult (≥18 years of age)
- All admitted patients with severe or critical COVID-19
- Confirmed diagnosis of COVID-19 through RT-PCR (attach report) and/or HRCT Chest
- Patients at high risk of coagulopathy demonstrating signs of micro-thrombi induced organ dysfunction or strongly suspected macro thromboembolism
Exclusion Criteria:
- High risk of bleeding as judged by treating physicians
- Contra-indication to therapeutic anti coagulation
- Platelets < 50,000 (attach report)
- INR >1.5
- Evidence of current or recent bleeding
Sites / Locations
- Rawalpindi Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Interventional Arm
Comparator/control
Arm Description
Ecru (Apixaban )Tablets
Rivascot (Rivaroxaban)
Outcomes
Primary Outcome Measures
Bleeding
The participants with bleeding episodes
Secondary Outcome Measures
Clotting
The participants with clotting incidences
Full Information
NCT ID
NCT05088928
First Posted
October 21, 2021
Last Updated
February 22, 2022
Sponsor
Scotmann Pharmaceuticals
Collaborators
Rawalpindi Medical College
1. Study Identification
Unique Protocol Identification Number
NCT05088928
Brief Title
Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care
Acronym
ECRU
Official Title
Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 1, 2022 (Anticipated)
Primary Completion Date
May 30, 2022 (Anticipated)
Study Completion Date
August 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Scotmann Pharmaceuticals
Collaborators
Rawalpindi Medical College
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to describe the safety and efficacy outcomes of a cohort of ICU patients with severe COVID-19 respiratory disease treated with therapeutic dose Apixaban for COVID-19 at a tertiary public health care setting.
Detailed Description
There is an increased risk of Venous and Arterial thromboembolism in COVID-19 infection. The main reason being that the novel coronavirus SARS-CoV-2 induces hyperinflammation and subsequently immunothrombolism which is wide spread in the body. The angiotensin converting enzyme 2 (ACE2) receptor, which is utilized by the virus to infect the host, is present throughout the human body organs and endothelial cells. Thrombotic microangiopathies are the consequence of this direct endothelial invasion of the virus and widespread endothelial inflammation. Consequently, pervasive dysfunction of the endothelium and apoptosis is seen primarily due to the host immune response and release of pro inflammatory cytokines.
A hypercoagulable state is therefore seen due to the shift in the vascular equilibrium towards a vasoconstrictive and inflammatory response, promoting a microvascular derangement and dysfunctions.
Although this pathological response is not unique to the COVID-19 disease, the systemic coagulopathies observed due to this novel virus are noted to be slightly distinct. These include the increased risk of mortality with the increased level of D-Dimers in nearly 50% of the patients . While mild prolongation of Prothrombin time and thrombocytopenia are not noted to be important predictors of the severity of the disease or its adverse outcomes .
In COVID-19 patients, the International Society on Thrombosis and Hemostasis (ISTH). criteria for Disseminated Intravascular Coagulation (DIC) is seldom met, despite the indication by the typical triad of thrombin time prolonged, decreased platelet counts and increased D-dimer levels .
Although the Disseminated Intravascular Coagulation is low grade, the fibrinolytic system is activated and endogenous tissue plasminogen is released because of the pathogenic inflammation-causing endothelial cell injury and thrombotic angiopathies of the microvascular system. This also contributes to the increased mortalities due to high D-Dimer levels.
WHAT IS KNOWN?
As high as 69% of COVID-19 patients under Critical Care have been reported to experience the incidence of complication related to thromboembolism .
Although the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) as anticoagulation prophylaxis has been observed with beneficial results in decreasing COVID-19 mortalities, however, there are reports of high incidences of thromboembolic complications despite the prophylaxis too.
Although prophylactic therapeutic anti coagulation has been reported with reduced incidences of venous thromboembolism (VTE) , a study has shown almost similar incidence of bleeding in the anticoagulation prophylaxis group as compared to the group which did not receive any anticoagulation (3 versus 1.9%, p = 0.20).
RATIONALE:
Since the link between COVID-19 related coagulopathies and mortalities has been established, it is of paramount importance to establish the optimal strategy. When compared to classical anticoagulants including Unfractioned Heparin, the comparatively newer salt of Apixaban belonging to the Direct Oral Anti Coagulants (DOACs) class, has been reported to have decreased rate of unwanted bleeding incidences, lower requirement of regular lab monitoring, fewer drug-drug interactions, increased pharmacokinetic (PK) and pharmacodynamic (PD) predictability and better efficacy .
Due to these advantages particularly the more predictable dose-response curve of Apixaban, its use has markedly increased in many generalized settings in hospitals since its approval. Apart from this, it is also being started in the Critical Units of COVID-19 and continued thereafter.
RELEVANCE, IMPORTANCE AND APPLICABILITY:
The investigators had particular interest in Apixaban in the COVID-19 setting because of the easy twice daily dosing regime, decreased need of regular lab monitoring, decreased room congestion, decreased medical staff exposure and consequently decreased need of Personal Protective Equipment among others. Nevertheless, the anti-inflammatory effects of Apixaban by decreasing plasma induced superoxide productions, are comparable to Unfractioned Heparin and Low Molecular Weight Heparin.
RESEARCH GAP IDENTIFIED:
Despite these numerous purported benefits, to the best of the investigators' knowledge, there are no published reports describing the clinical outcomes of apixaban use in critically ill ICU patients with severe COVID-19 , in Pakistan.
PURPOSE OF STUDY:
As such, the purpose of this study is to describe the safety and efficacy outcomes of a cohort of ICU patients with severe COVID-19 respiratory disease treated with therapeutic dose apixaban for COVID-19 at a tertiary public health care setting.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Anticoagulation, Apixaban
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Interventional Arm
Arm Type
Experimental
Arm Description
Ecru (Apixaban )Tablets
Arm Title
Comparator/control
Arm Type
Active Comparator
Arm Description
Rivascot (Rivaroxaban)
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
ECRU Tablets
Intervention Description
Direct Acting Oral Anti coagulant
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
Rivascot tablets
Intervention Description
Direct Acting Oral Anti coagulant
Primary Outcome Measure Information:
Title
Bleeding
Description
The participants with bleeding episodes
Time Frame
10 days
Secondary Outcome Measure Information:
Title
Clotting
Description
The participants with clotting incidences
Time Frame
10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult (≥18 years of age)
All admitted patients with severe or critical COVID-19
Confirmed diagnosis of COVID-19 through RT-PCR (attach report) and/or HRCT Chest
Patients at high risk of coagulopathy demonstrating signs of micro-thrombi induced organ dysfunction or strongly suspected macro thromboembolism
Exclusion Criteria:
High risk of bleeding as judged by treating physicians
Contra-indication to therapeutic anti coagulation
Platelets < 50,000 (attach report)
INR >1.5
Evidence of current or recent bleeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Prof. Dr. Muhammad Umar, MBBS
Phone
0092519281011
Email
info@rmur.edu.pk, syedasabaaslam@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Prof. Dr. Fazl ur Rehman Rehman, MBBS
Phone
00923005226950
Email
lonsa25@student.london.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. Dr. Muhammad Umar, MBBS
Organizational Affiliation
Rawalpindi Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rawalpindi Medical University
City
Rawalpindi
State/Province
Punjab
Country
Pakistan
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Imran Arshad, MBBS
Phone
00923455060296
Email
lonsa25@student.london.ac.uk
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Proformas
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Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care
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