Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care

NCT ID: NCT05088928

Last Updated: 2022-03-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2022-08-30

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional Arm

Ecru (Apixaban )Tablets

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

Direct Acting Oral Anti coagulant

Comparator/control

Rivascot (Rivaroxaban)

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

Direct Acting Oral Anti coagulant

Interventions

Apixaban

Direct Acting Oral Anti coagulant

Intervention Type: DRUG

Rivaroxaban

Direct Acting Oral Anti coagulant

Intervention Type: DRUG

Other Intervention Names

ECRU Tablets; Rivascot tablets

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rawalpindi Medical College

OTHER

Sponsor Role: collaborator

Scotmann Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Dr. Syeda Saba Aslam

Head of Medical Affairs

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prof. Dr. Muhammad Umar, MBBS

Role: PRINCIPAL_INVESTIGATOR

Rawalpindi Medical College

Locations

Rawalpindi Medical University

Rawalpindi, Punjab Province, Pakistan

Countries

Pakistan

Central Contacts

Prof. Dr. Muhammad Umar, MBBS

Role: CONTACT

info@rmur.edu.pk, syedasabaaslam@gmail.com

0092519281011

Prof. Dr. Fazl ur Rehman Rehman, MBBS

Role: CONTACT

lonsa25@student.london.ac.uk

00923005226950

Facility Contacts

Imran Arshad, MBBS

Role: primary

lonsa25@student.london.ac.uk

00923455060296

Other Identifiers

U1111-1272-7249

Identifier Type: REGISTRY

Identifier Source: secondary_id

RMUSCOTMANNECRUTRIAL

Identifier Type: -

Identifier Source: org_study_id