Early Prophylactic Low-molecular-weight Heparin (LMWH) in Symptomatic COVID-19 Positive Patients (ETHIC)

April 26, 2022 updated by: Thrombosis Research Institute

Early Thromboprophylaxis in COVID-19 (ETHIC Trial): an Open Label, Randomized Phase IIIb Trial of Community-based (LMWH) Versus Standard of Care (no Enoxaparin) in COVID-19 Positive Patients

Evidence has shown that COVID-19 infections can lead to an increased risk of blood clots. These blood clots can lead to individuals being admitted to hospital, or, unfortunately in severe cases, death. Enoxaparin is a blood-thinning drug which has been used by doctors and nurses in hospitals for many years to prevent the thickening of blood which may lead to a clot. It is easier for doctors to prevent new blood clots from forming than treating existing blood clots.

Currently, there are no treatments for COVID-19. There is an urgent need to find a safe and effective treatment to prevent worsening of the disease that may lead to hospital admission and/or death. The ETHIC (Early Thromboprophylaxis in COVID-19) study aims to find out if giving enoxaparin in an early stage of the COVID-19 disease can prevent individuals being admitted to hospital and/or death. The study will take place in approximately 8 to 10 countries, in approximately 30 to 50 centres.

Patients will be allowed to take part if they have had a confirmed COVID-19 infection, are ≥ 55 years of age and have at least two of the following additional risk factors; age ≥ 70 years, body mass index > 25 kg/m2, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, or corticosteroid use.

Half the patients in the study will receive the blood-thinning drug enoxaparin for three weeks, and half will receive no treatment. Individuals will be randomly allocated to one of these groups. After 21 days, the number of patients in each group who were either admitted to hospital, or died, will be compared. The number of patients in each group who developed a blood clot (venous thromboembolism) will also be compared. Further comparisons will be made at both 50 and 90 days after the beginning of the study.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is an open label randomized controlled trial of symptomatic individuals with confirmed COVID-19 in a community setting.

Justification: There is currently no standard of care treatment for Covid-19.

Upon enrolment into the study, patients will be randomised to receive either enoxaparin (40 mg once per day if < 100 kg, 40 mg twice per day if ≥ 100 kg) or the current standard of care (no enoxaparin) for three weeks (21 days). Randomisation must occur within 5 days of the SARS-CoV-2 test. Data will be collected at baseline and 21 days, with further assessments at 50 and 90 days.

Participants randomised to enoxaparin will receive pre-loaded syringes as part of the study, and information regarding self-administration will be provided by the sponsor. Participants in the control arm of this study will receive no treatment (current standard of care).

Screening Phase:

Investigator sites will be selected to represent community care in each country (from general practice/office based care settings, testing centres and hospitals) and invited to participate. All individuals satisfying the inclusion/exclusion criteria will be considered for enrolment and their medical history checked to exclude any patients not suitable.

Participants will be provided with a patient information sheet and consent form (PISCF), either paper or an electronic version. All participants must provide informed consent by reviewing and discussing the PISCF and by completing and signing the consent form (paper version or the electronic version). Once informed consent has been obtained, data related to baseline will be collected from a review of the participants' medical records and entered into the electronic data capture system.

Treatment Phase:

Data related to clinical outcomes for both the primary outcome (composite of hospitalisation and/or death) and secondary safety outcome (major bleeding) will be measured at 21 days. This time point will be used as a marker for collection of all data from the preceding period.

Safety and Monitoring Phase:

Data related to all outcomes will be again measured at 50 days. This time point will be used as a marker for collection of all data from the preceding period to evaluate the incidence of bleeding in all participants.

End of Study and Follow-up Phase:

The outcomes of death and hospitalisation will be further recorded 90 days after randomisation. This time point will be used as a marker for collection of all information from the interim period. The end of the trial will occur immediately following the last visit/data item of the last patient undergoing the trial. The aim of data collection will be to accurately capture all planned and unplanned visits, interruptions to treatment and events.

In case no patient data have been recorded in the participant's medical records at the site during the months following the last data entry, a follow-up phone contact will be made by the site and documented to verify that all events are being captured and participants are not lost to follow up.

The schedule of assessments is as follows: Reference: Section 6.5 of the protocol. Pages 27 to 29.

Study Type

Interventional

Enrollment (Actual)

219

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • Australia
      • Melbourne, Australia
        • Harry Gibbs, National Co-ordinating Investigator, The Alfred Hospital
  • Belgium
      • Brasschaat, Belgium
        • Dr Frank Cools, National Co-ordinating Investigator, AZ Klina
  • South Africa
      • Johannesburg, South Africa
        • Prof. Barry Jacobson, National Coordinating Investigator, University of the Witwatersrand

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

Ages Eligible for Study

55 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed Informed consent
  • Confirmed COVID-19 (i.e. symptoms + positive test for SARS-CoV-2)
  • Male or female, age ≥ 55 years
  • At least two of the following additional risk factors:

Age ≥ 70 years Body mass index > 25 kg/m2 Chronic obstructive pulmonary disease (COPD)* Diabetes* Cardiovascular disease* Corticosteroid use

*Defined as any disease requiring medical intervention or treatment.

Exclusion Criteria:

  • Contraindications to unfractionated heparin or LMWH
  • Recent (<48 hours) or planned spinal or epidural anesthesia or puncture, PCI or thrombolytic therapy within the preceding 24 hours
  • Increased risk for bleeding complications
  • Pregnant women
  • Severe renal impairment (GFR < 30 mL/min)
  • Receiving any antiplatelet therapy (with the exception of low dose (≤100mg) aspirin) or anticoagulant therapy (e.g. VKA, DOAC)
  • Patients participating in an interventional study that is outside the purview of TRI sponsored studies.

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
Intervention / Treatment
EXPERIMENTAL: Enoxaparin
(40 mg o/d if < 100 kg, 40 mg b/d if ≥ 100 kg)
Drug: Enoxaparin
The treatment provided will be enoxaparin sodium 40mg/0.4 mL. All doses will be provided in pre-filled, single-dose syringes for subcutaneous injection.
Other Names:
  • Lovenox/Clexane
NO_INTERVENTION: Current standard of care (no enoxaparin)
Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital Admission
Time Frame: 21 days

Hospital admission including:

Pneumonia Acute Respiratory distress syndrome Admission to intensive care unit (ICU) Mechanical ventilation (MV)/intubation requirement Continuous positive airway pressure (CPAP)/Non-invasive ventilation Extracorporeal membrane oxygenation (ECMO)
21 days
Hospital Admission
Time Frame: 50 days

Hospital admission including:

Pneumonia Acute Respiratory distress syndrome Admission to intensive care unit (ICU) Mechanical ventilation (MV)/intubation requirement Continuous positive airway pressure (CPAP)/Non-invasive ventilation Extracorporeal membrane oxygenation (ECMO)
50 days
Hospital Admission
Time Frame: 90 days

Hospital admission including:

Pneumonia Acute Respiratory distress syndrome Admission to intensive care unit (ICU) Mechanical ventilation (MV)/intubation requirement Continuous positive airway pressure (CPAP)/Non-invasive ventilation Extracorporeal membrane oxygenation (ECMO)
90 days
Death
Time Frame: 21 days
All-cause Cardiovascular Non-Cardiovascular Specific causes Fatal bleed
21 days
Death
Time Frame: 50 days
All-cause Cardiovascular Non-Cardiovascular Specific causes Fatal bleed
50 days
Death
Time Frame: 90 days
All-cause Cardiovascular Non-Cardiovascular Specific causes Fatal bleed
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bleeding (as defined by ISTH criteria)
Time Frame: 21 and 50 days
Frequency Location Treatment (transfusion and units of blood products transfused) Severity (classified as major, clinically relevant non-major and minor)
21 and 50 days
Diagnosis of VTE
Time Frame: 21, 50 and 90 days
Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
21, 50 and 90 days

Collaborators and Investigators

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

Sponsor

Thrombosis Research Institute

Collaborators

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (ACTUAL)

October 27, 2020

Primary Completion (ACTUAL)

November 29, 2021

Study Completion (ACTUAL)

November 29, 2021

Study Registration Dates

First Submitted

July 22, 2020

First Submitted That Met QC Criteria

July 29, 2020

First Posted (ACTUAL)

July 30, 2020

Study Record Updates

Last Update Posted (ACTUAL)

May 2, 2022

Last Update Submitted That Met QC Criteria

April 26, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRI-08892
  • 2020-003125-39 (EUDRACT_NUMBER)

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

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