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Covid19Phase 3EMOS-COVIDNCT04646655

Enoxaparin at Prophylactic or Therapeutic Doses in COVID-19

A Phase 3 study testing Enoxaparin in people with Covid19 and Thrombosis, run by ASST Fatebenefratelli Sacco at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Covid19, Thrombosis
What is being tested?
Enoxaparin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
142 participants
Where
1 siteItaly
Study dates
27 Jul 2020to 30 Apr 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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]
Show all 16Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • ASST Fatebenefratelli Sacco

    Milan, 20157

Other trials in Italy

About this study

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

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).

Read the 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.

Conditions
Covid19, Thrombosis
Being tested
Enoxaparin
Keywords
COVID.19, Thrombosis, Enoxaparin, Outcome, Respiratory failure, D-dimer, Venous compression ultrasound
Medical subject headings
COVID-19, Thrombosis, Respiratory Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnoxaparinDrug

    Also called Clexane

    subcutaneous injections

Study groups in NCT04646655
Study groupRoleWhat they receive
Enoxaparin at prophylactic doseActive comparatorEnoxaparin at prophylactic dose: standard 4.000 IU QD via subcutaneous injection (6000 IU if body weight>100 kg)
Receives: Drug: Enoxaparin
Enoxaparin at therapeutic doseExperimentalEnoxaparin 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
Receives: Drug: Enoxaparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality rate

    Mortality registered during the time frame

    Measured: 30 days from enrollment

  2. Progression of respiratory failure

    Progression of respiratory failure defined as duration of continuous positive pressure ventilation (CPAP)

    Measured: 30 days from enrollment

  3. Progression of respiratory failure

    Progression of respiratory failure defined as percentage of patients admitted to ICU

    Measured: 30 days from enrollment

  4. Progression of respiratory failure

    Progression of respiratory failure defined as percentage of patients undergoing oro-tracheal intubation

    Measured: 30 days from enrollment

  5. Number of major bleeding episodes

    Major bleeding (ISTH criteria) and/or clinically relevant non-major bleeding

    Measured: up to 6 months from randomization

Secondary outcomes (4)

  1. Respiratory function improvement

    Amelioration of the respiratory function defined as a PaO2/FiO2 increase > 300 and / or respiratory rate (RR) < 20 breaths per min

    Measured: at 72 hours

  2. Respiratory function improvement

    Amelioration of the respiratory function defined as a PaO2/FiO2 increase > 300 and / or respiratory rate (RR) < 20 breaths per min

    Measured: 1 week from randomization

  3. Number of major cardiovascular events

    numbers of myocardial infarction and stroke within the time frame

    Measured: 6 months from randomization

  4. Deep Vein Thrombosis

    Numbers of Deep Vein Thrombosis at CUS examination within the time frame

    Measured: 6 months from randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2020
  2. Study start27 Jul 2020
  3. Primary completion16 Oct 2022
  4. Study completion30 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04646655
Sponsor's protocol ID
HLS-02COVID19/2020
Acronym
EMOS-COVID
Status last verified
Jul 2023
First submitted
22 Nov 2020
Last updated
25 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020 Jun 25;58(7):1116-1120. doi: 10.1515/cclm-2020-0188.

    PubMed 32172226

  • Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.

    PubMed 32073213

  • Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

    PubMed 32171076

  • Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.

    PubMed 32167524

  • Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

    PubMed 32007143

  • McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537. Epub 2020 Apr 3.

    PubMed 32251717

  • Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27.

    PubMed 32220112

  • Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017 Sep 27;7(9):e017046. doi: 10.1136/bmjopen-2017-017046.

    PubMed 28963294

  • Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res. 2008;122(6):743-52. doi: 10.1016/j.thromres.2006.10.026. Epub 2007 Aug 28.

    PubMed 17727922

  • Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017 Feb 28;117(3):437-444. doi: 10.1160/TH16-08-0620. Epub 2016 Dec 15.

    PubMed 27975101

  • Mousavi S, Moradi M, Khorshidahmad T, Motamedi M. Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review. Adv Pharmacol Sci. 2015;2015:507151. doi: 10.1155/2015/507151. Epub 2015 May 12.

    PubMed 26064103

  • Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020 May;18(5):1020-1022. doi: 10.1111/jth.14821. Epub 2020 Apr 27. No abstract available.

    PubMed 32239799

  • Milewska A, Zarebski M, Nowak P, Stozek K, Potempa J, Pyrc K. Human coronavirus NL63 utilizes heparan sulfate proteoglycans for attachment to target cells. J Virol. 2014 Nov;88(22):13221-30. doi: 10.1128/JVI.02078-14. Epub 2014 Sep 3.

    PubMed 25187545

  • Barrett CD, Moore HB, Yaffe MB, Moore EE. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: A comment. J Thromb Haemost. 2020 Aug;18(8):2060-2063. doi: 10.1111/jth.14860. Epub 2020 Jun 14. No abstract available.

    PubMed 32302462

  • Wada H, Thachil J, Di Nisio M, Mathew P, Kurosawa S, Gando S, Kim HK, Nielsen JD, Dempfle CE, Levi M, Toh CH; The Scientific Standardization Committee on DIC of the International Society on Thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013 Feb 4. doi: 10.1111/jth.12155. Online ahead of print.

    PubMed 23379279

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enoxaparin in people with Covid19 and Thrombosis, run by ASST Fatebenefratelli Sacco at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality rate (time frame: 30 days from enrollment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04646655, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2023.

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