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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04646655
Recruitment Status : Recruiting
First Posted : November 30, 2020
Last Update Posted : November 30, 2020
Sponsor:
Collaborators:
Massimo Arquati
Riccardo Colombo
Umberto Russo
Manuela Nebuloni
Spinello Antinori
Information provided by (Responsible Party):
Maddalena Alessandra Wu, ASST Fatebenefratelli Sacco

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Covid19 Thrombosis Drug: Enoxaparin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 27, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Clots

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 Name: 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 Name: Clexane




Primary Outcome Measures :
  1. Mortality rate [ Time Frame: 30 days from enrollment ]
    Mortality registered during the time frame

  2. Progression of respiratory failure [ Time Frame: 30 days from enrollment ]
    Progression of respiratory failure defined as duration of continuous positive pressure ventilation (CPAP)

  3. Progression of respiratory failure [ Time Frame: 30 days from enrollment ]
    Progression of respiratory failure defined as percentage of patients admitted to ICU

  4. Progression of respiratory failure [ Time Frame: 30 days from enrollment ]
    Progression of respiratory failure defined as percentage of patients undergoing oro-tracheal intubation

  5. Number of major bleeding episodes [ Time Frame: up to 6 months from randomization ]
    Major bleeding (ISTH criteria) and/or clinically relevant non-major bleeding


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Number of major cardiovascular events [ Time Frame: 6 months from randomization ]
    numbers of myocardial infarction and stroke within the time frame

  4. Deep Vein Thrombosis [ Time Frame: 6 months from randomization ]
    Numbers of Deep Vein Thrombosis at CUS examination within the time frame



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04646655


Contacts
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Contact: Maddalena A Wu, M.D. +390239041 maddalena.ale.wu@gmail.com
Contact: Massimo Arquati, M.D. +390239041 arquati.massimo@gmail.com

Locations
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Italy
ASST Fatebenefratelli Sacco Recruiting
Milan, Italy, 20157
Contact: Maddalena A Wu, M.D.    +393392883379    maddalena.ale.wu@gmail.com   
Sponsors and Collaborators
ASST Fatebenefratelli Sacco
Massimo Arquati
Riccardo Colombo
Umberto Russo
Manuela Nebuloni
Spinello Antinori
Investigators
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Principal Investigator: Maddalena A Wu, M.D. ASST Fatebenefratelli Sacco
Publications:

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Responsible Party: Maddalena Alessandra Wu, Principal Investigator, ASST Fatebenefratelli Sacco
ClinicalTrials.gov Identifier: NCT04646655    
Other Study ID Numbers: HLS-02COVID19/2020
First Posted: November 30, 2020    Key Record Dates
Last Update Posted: November 30, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maddalena Alessandra Wu, ASST Fatebenefratelli Sacco:
COVID.19
Thrombosis
Enoxaparin
Outcome
Respiratory failure
D-dimer
Venous compression ultrasound
Additional relevant MeSH terms:
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Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Enoxaparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action