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COVIDPhase 4COVI-DOSENCT04373707

Weight-Adjusted vs Fixed Low Doses of Low Molecular Weight Heparin For Venous Thromboembolism Prevention in COVID-19

A Phase 4 study testing Enoxaparin in people with COVID and Thrombosis, run by Central Hospital, Nancy, France at 17 sites in France.

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

Worldwide observational studies indicate a significant prothrombogenic effect associated with SARS-CoV-2 infection with a high incidence of venous thromboembolism (VTE), notably life-threatening pulmonary embolism. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID, Thrombosis, Pulmonary Embolism
What is being tested?
Enoxaparin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,000 participants
Where
17 sitesFrance
Study dates
13 May 2020to 14 Sep 2021
Phase
Phase 4
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patient hospitalized for a probable/confirmed COVID-19 infection (confirmed by serology/polymerase chain reaction or by radiologic signs of COVID-19 pneumonia in the setting of clinical and laboratory abnormalities suggestive of a SARS-CoV-2 infection)
  • Signed informed consent
  • Patient affiliated to the Social Security

Who cannot join

  • Renal insufficiency with a GFR<15 mL/min/1.73m²
  • Acute kidney injury KDIGO3
  • Prophylactic dose of low molecular weight heparin for more than 3 days
  • Curative dose of low molecular weight heparin for more than 1 day
  • Recurrent catheter/hemodialysis access thromboses
  • ECMO required in the next 24h
Show all 13Show fewer
  • Contraindication to low molecular weight heparin
  • High bleeding risk (e.g. uncontrolled severe systemic hypertension, recent major bleeding, disseminated intravascular coagulopathy, thrombocytopenia < 75G/L)
  • History of heparin-induced thrombocytopenia
  • Contraindication to blood-derived products
  • Impossibility to perform a doppler ultrasound of the lower limbs (e.g. above the knee amputation, severe burn injuries)
  • Expected death in the next 48h
  • Vulnerable subjects according to articles L. 1121-5, L. 1121-7 et L1121-8 of French Public Health Code

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

France17 sites

  • Amiens Academic Hospital

    Amiens

  • Besançon Academic Hospital

    Besançon

  • Brest Academic Hospital

    Brest

  • Civil Hospital

    Colmar

  • Dijon Academic Hospital

    Dijon

  • Kremlin Bicêtre Academic Hospital

    Le Kremlin-Bicêtre

  • Lille Academic Hospital

    Lille

  • Groupe Hospitalier Unéos

    Metz

  • Metz-Thionville Regional Hospital

    Metz

  • Montpellier Academic Hospital

    Montpellier

  • Emile Muller Hospital

    Mulhouse

  • Nancy Academic Hospital

    Nancy

  • George Pompidou European Hospital

    Paris

  • Lariboisière Academic Hospital

    Paris

  • St Etienne Academic Hospital

    Saint-Etienne

  • Strasbourg Academic Hospital

    Strasbourg

  • Toulouse Academic Hospital

    Toulouse

Other trials in France

About this study

Official title: Effectiveness of Weight-adjusted Prophylactic Low Molecular Weight Heparin Doses Compared With Lower Fixed Prophylactic Doses to Prevent Venous Thromboembolism in COVID-2019. The Multicenter Randomized Controlled Open-label Trial COVI-DOSE

Worldwide observational studies indicate a significant prothrombogenic effect associated with SARS-CoV-2 infection with a high incidence of venous thromboembolism (VTE), notably life-threatening pulmonary embolism.

According to recommendations for acute medical illnesses, all COVID-19 hospitalized patients should be given VTE prophylaxis such as a low molecular weight heparin (LMWH). A standard prophylactic dose (eg. Enoxaparin 4000IU once daily) could be insufficient in obese patients and VTE has been reported in patients treated with a standard prophylactic dose.

Read more

In COVID-19 patients, guidelines from several international societies confirm the existence of an hypercoagulability and the importance of thromboprophylaxis but the "optimal dose is unknown" and comparative studies are needed.

In view of these elements, carrying out a trial comparing various therapeutic strategies for the prevention of VTE in hospitalized patients with COVID-19 constitutes a health emergency.

Thus, we hypothesize that an increased prophylactic dose of weight-adjusted LMWH would be greater than a lower prophylactic dose of LMWH to reduce the risk of life-threatening VTE in hospitalized patients. The benefit-risk balance of this increase dose will be carefully evaluated because of bleeding complications favored by possible renal / hepatic dysfunctions, drug interactions or invasive procedures in COVID-19 patients.

This multicenter randomized (1:1) open-label controlled trial will randomize hospitalized adults with COVID-19 infection to weight-adjusted prophylactic dose vs. lower prophylactic dose of LMWH.

Being tested
Enoxaparin
Keywords
COVID, Thrombosis, Venous Thromboembolism, Pulmonary Embolism, Deep Vein Thrombosis, Low Molecular Weight Heparin
Medical subject headings
Thrombosis, Pulmonary Embolism, Venous Thrombosis, Venous Thromboembolism

What participants receive

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

  • EnoxaparinDrug

    Also called Tinzaparin, Nadroparin, Dalteparin

    For example (Enoxaparin):

    • 4000IU twice a day in patients <50kg
    • 5000IU twice a day in patients 50-70kg
    • 6000IU twice a day in patients 70-100kg
    • 7000IU twice a day in patients above 100kg

  • EnoxaparinDrug

    Also called Tinzaparin, Nadroparin, Dalteparin

    For example (Enoxaparin): From 4000IU once a day in patients admitted in medical ward to 4000IU twice a day in patients admitted in the ICU. In patients with severe renal insufficiency (GFR=15-30 mL/min/1.73m²), LMWH doses will be reduced by 50%.

Study groups in NCT04373707
Study groupRoleWhat they receive
Low Prophylactic Dose of Low Molecular Weight HeparinActive comparatorEnoxaparin, Tinzaparin, Nadroparin, Dalteparin
Receives: Drug: Enoxaparin
Weight-Adjusted Prophylactic Dose Low Molecular Weight HeparinExperimentalEnoxaparin, Tinzaparin, Nadroparin, Dalteparin
Receives: Drug: Enoxaparin

What is being measured

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

  1. Venous thromboembolism

    Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death

    Measured: hospitalization stay (up to 28 days)

Secondary outcomes (7)

  1. Major bleeding

    Risk of major bleeding defined by the ISTH

    Measured: hospitalization stay (up to 28 days)

  2. Major Bleeding and Clinically Relevant Non-Major Bleeding

    Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH

    Measured: hospitalization stay (up to 28 days)

  3. Net Clinical Benefit

    Risk of Venous Thromboembolism and Major Bleeding

    Measured: hospitalization stay (up to 28 days) and 60 days

  4. Venous Thromboembolism at other sites

    Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb

    Measured: hospitalization stay (up to 28 days)

  5. Arterial Thrombosis

    Risk of arterial thrombosis at any sites

    Measured: hospitalization stay (up to 28 days)

  6. All-Cause Mortality

    Risk of all-cause mortality

    Measured: hospitalization stay (up to 28 days) and 60 days

  7. Factors associated with the risk of venous thromboembolism

    Identification of associations between the risk of venous thromboembolism and clinical (eg. past medical history of thrombosis, cardiovascular risk factors, treatments, severity of COVID-19) and laboratory variables (e.g. D-dimers, fibrinogen, CRP) collected in the eCRF

    Measured: hospitalization stay (up to 28 days)

Timeline

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

  1. First posted4 May 2020
  2. Study start13 May 2020
  3. Primary completion29 Apr 2021
  4. Study completion14 Sep 2021

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 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicenter randomized (1:1) controlled open-label trial, stratified on disease severity (admission to ICU or not)
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,000 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04373707
Sponsor's protocol ID
2020-001709-21
Acronym
COVI-DOSE
Status last verified
Aug 2023
First submitted
1 May 2020
Last updated
7 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zuily S, Lefevre B, Sanchez O, Empis de Vendin O, de Ciancio G, Arlet JB, Khider L, Terriat B, Greigert H, Robert CS, Louis G, Trinh-Duc A, Rispal P, Accassat S, Thiery G, Montani D, Azarian R, Meneveau N, Soudet S, Le Mao R, Maurier F, Le Moing V, Quere I, Yelnik CM, Lefebvre N, Martinot M, Delrue M, Benhamou Y, Parent F, Roy PM, Presles E, Goehringer F, Mismetti P, Bertoletti L, Rossignol P, Couturaud F, Wahl D, Thilly N, Laporte S; COVI-DOSE investigators. Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial. EClinicalMedicine. 2023 Jun;60:102031. doi: 10.1016/j.eclinm.2023.102031. Epub 2023 Jun 9.

    PubMed 37350990

  • Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

    PubMed 35244208

  • Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

    PubMed 33502773

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Enoxaparin in people with COVID and Thrombosis, run by Central Hospital, Nancy, France at 17 sites in France.

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 3 inclusion and 13 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 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Venous thromboembolism (time frame: hospitalization stay (up to 28 days)). 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 NCT04373707, which also lists 3 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 7 Aug 2023.

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