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

February 22, 2022 updated by: Dr. Syeda Saba Aslam, Scotmann Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Interventional Arm
Ecru (Apixaban )Tablets
Drug: Apixaban
Direct Acting Oral Anti coagulant
Other Names:
  • ECRU Tablets
ACTIVE_COMPARATOR: Comparator/control
Rivascot (Rivaroxaban)
Drug: Rivaroxaban
Direct Acting Oral Anti coagulant
Other Names:
  • Rivascot tablets

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Bleeding
Time Frame: 10 days
The participants with bleeding episodes
10 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clotting
Time Frame: 10 days
The participants with clotting incidences
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Scotmann Pharmaceuticals

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Rawalpindi Medical College

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Prof. Dr. Muhammad Umar, MBBS, Rawalpindi Medical College

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2022

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 30, 2022

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 21, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2021

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 22, 2021

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RMUSCOTMANNECRUTRIAL
  • U1111-1272-7249 (REGISTRY: ICTRP, WHO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Proformas

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on COVID-19

Clinical Trials on Apixaban

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings