Enoxaparin at Prophylactic or Therapeutic Doses in COVID-19 (EMOS-COVID)

July 22, 2023 updated by: Maddalena Alessandra Wu, ASST Fatebenefratelli Sacco

Enoxaparin at Prophylactic or Therapeutic Doses With Monitoring of Outcomes in Subjects Infected With COVID-19: a Pilot Study on 300 Cases Enrolled at ASST-FBF-Sacco

SINGLE CENTER PHASE III INTERVENTIONAL RANDOMIZED CONTROLLED TRIAL comparing efficacy and safety of enoxaparin at prophylactic dose (standard treatment) and enoxaparin at therapeutic dose (OFF-LABEL treatment) in 300 COVID-19 infected patients with moderate-severe respiratory failure (PaO2/FiO2<250) and/or increased D-dimer levels enrolled in different Units (Infectious disease, Internal Medicine, Emergency Medicine, Pneumology) of Azienda Socio Sanitaria Territoriale Fatebenefratelli Sacco (ASST-FBF-SACCO).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients with COVID-19 are at high risk of developing a venous thromboembolism (VTE) and it is essential that effective thromboprophylaxis with parenteral drugs (LMWH, UFH) is considered for all patients admitted to hospital especially in case of severe pneumonia.

The aim of the study is the evaluation of efficacy and safety of enoxaparin at prophylactic dose (standard treatment) as compared to enoxaparin at therapeutic dose (OFF-LABEL treatment) in 300 COVID-19 infected patients with moderate-severe respiratory failure (PaO2/FiO2<250) and/or increased D-dimer levels.

After the admission to different Units (Infectious disease, Internal Medicine, Emergency Medicine, Pneumology), enoxaparin at prophylactic dose (standard of care) will be prescribed to all patients.

The randomization of the single patient will be made when the the inclusion criteria (PaO2/FiO2 <250 and/or D-dimer >2000 ng/) will be satisfied. Patients with increased bleeding risk will be excluded (exclusion criteria).

Patients will be divided into two arms:

  • arm A: enoxaparin at prophylactic dose (standard 4.000 IU; 6000 UI if body weight>100 kg)
  • arm B: enoxaparin at therapeutic dose (70 U/Kg b.i.d. every 12 h)

In both arms, enoxaparin treatment will be monitored clinically and with first and second line laboratory tests Venous compression ultrasound (CUS) will be performed at admission and after 7 days in case of a first negative exam and elevated D-Dimer levels, to rule out deep vein thrombosis.

Enoxaparin at prophylactic dose (4000 IU) will be maintained in all patients for 4 weeks after discharge.

Study Type

Interventional

Enrollment (Actual)

142

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

  • Italy
      • Milan, Italy, 20157
        • Asst Fatebenefratelli Sacco

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • COVID-19 related pneumonia with moderate-severe respiratory failure (PaO2/FiO2<250) and/or markedly increased D-dimer level (>2000 ng/mL)
  • Signed informed consent

Exclusion Criteria:

  • age < 18 and > 80 yrs
  • history of bleeding (peptic ulcer, esophageal varices, cerebral aneurysm, cancer at high risk of bleeding, cirrhosis, hemorrhagic stroke < 1 year)
  • thrombocytopenia (<100 x109/L)
  • anemia (Hb < 8 g/dl)
  • coagulation abnormalities (PT e/o aPTT > 1.5; fibrinogen < 150 mg/dl)
  • consumption coagulopathy (ISTH criteria) [15, 16]
  • deep vein thrombosis or pulmonary embolism
  • dual antiplatelet therapy
  • ongoing anticoagulant therapy
  • allergic reaction to LMWH
  • previous heparin-induced thrombocytopenia
  • major surgery < 1 month; neurosurgery <3 months; eye surgery <3 months
  • pregnancy
  • arterial hypertension (SBPS>160 mm Hg; DBP>100 mm Hg)
  • renal failure (creatinine clearance 30 ml/min)
  • ICU admission or endotracheal intubation

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Enoxaparin at prophylactic dose
Enoxaparin at prophylactic dose: standard 4.000 IU QD via subcutaneous injection (6000 IU if body weight>100 kg)
Drug: Enoxaparin
subcutaneous injections
Other Names:
  • Clexane
Experimental: Enoxaparin at therapeutic dose

Enoxaparin at therapeutic dose : 70 U/Kg b.i.d. (every 12 h)

In order to easily calculate the correct therapeutic dose of enoxaparin for each patient, a simplified categorization will be applied, as follows:

  • weight < 65 Kg: 4.000 IU b.i.d. (every 12 h)
  • weight ≥ 65 Kg: 6.000 IU b.i.d. (every 12 h)
  • weight ≥ 100 Kg: 8.000 IU b.i.d. (every 12 h) The most appropriate dose will be evaluated in patients with creatinine clearance between 30 and 50 ml/min
Drug: Enoxaparin
subcutaneous injections
Other Names:
  • Clexane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality rate
Time Frame: 30 days from enrollment
Mortality registered during the time frame
30 days from enrollment
Progression of respiratory failure
Time Frame: 30 days from enrollment
Progression of respiratory failure defined as duration of continuous positive pressure ventilation (CPAP)
30 days from enrollment
Progression of respiratory failure
Time Frame: 30 days from enrollment
Progression of respiratory failure defined as percentage of patients admitted to ICU
30 days from enrollment
Progression of respiratory failure
Time Frame: 30 days from enrollment
Progression of respiratory failure defined as percentage of patients undergoing oro-tracheal intubation
30 days from enrollment
Number of major bleeding episodes
Time Frame: up to 6 months from randomization
Major bleeding (ISTH criteria) and/or clinically relevant non-major bleeding
up to 6 months from randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Respiratory function improvement
Time Frame: at 72 hours
Amelioration of the respiratory function defined as a PaO2/FiO2 increase > 300 and / or respiratory rate (RR) < 20 breaths per min
at 72 hours
Respiratory function improvement
Time Frame: 1 week from randomization
Amelioration of the respiratory function defined as a PaO2/FiO2 increase > 300 and / or respiratory rate (RR) < 20 breaths per min
1 week from randomization
Number of major cardiovascular events
Time Frame: 6 months from randomization
numbers of myocardial infarction and stroke within the time frame
6 months from randomization
Deep Vein Thrombosis
Time Frame: 6 months from randomization
Numbers of Deep Vein Thrombosis at CUS examination within the time frame
6 months from randomization

Collaborators and Investigators

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

Sponsor

ASST Fatebenefratelli Sacco

Collaborators

Massimo Arquati
Riccardo Colombo
Umberto Russo
Manuela Nebuloni
Spinello Antinori

Investigators

  • Principal Investigator: Maddalena A Wu, M.D., Asst Fatebenefratelli Sacco

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)

July 27, 2020

Primary Completion (Actual)

October 16, 2022

Study Completion (Actual)

April 30, 2023

Study Registration Dates

First Submitted

November 22, 2020

First Submitted That Met QC Criteria

November 25, 2020

First Posted (Actual)

November 30, 2020

Study Record Updates

Last Update Posted (Actual)

July 25, 2023

Last Update Submitted That Met QC Criteria

July 22, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLS-02COVID19/2020

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

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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