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

NCT ID: NCT04492254

Last Updated: 2022-05-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-27
• Study Completion Date: 2021-11-29

Brief Summary

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.

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.

Conditions

COVID-19

Study Design

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

Study Groups

Enoxaparin

(40 mg o/d if \< 100 kg, 40 mg b/d if ≥ 100 kg)

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

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.

Current standard of care (no enoxaparin)

Standard of care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Lovenox/Clexane

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Thrombosis Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajay Kakkar

Role: STUDY_DIRECTOR

Thrombosis Research Institute

Locations

Harry Gibbs, National Co-ordinating Investigator, The Alfred Hospital

Melbourne, , Australia

Dr Frank Cools, National Co-ordinating Investigator, AZ Klina

Brasschaat, , Belgium

Prof. Barry Jacobson, National Coordinating Investigator, University of the Witwatersrand

Johannesburg, , South Africa

Countries

Australia; Belgium; South Africa

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Other Identifiers

2020-003125-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TRI-08892

Identifier Type: -

Identifier Source: org_study_id