NCT04373707

Brief 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. 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,000

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started May 2020

Geographic Reach
1 country

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 1, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 4, 2020

Completed
9 days until next milestone

Study Start

First participant enrolled

May 13, 2020

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 29, 2021

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 14, 2021

Completed
Last Updated

August 7, 2023

Status Verified

August 1, 2023

Enrollment Period

12 months

First QC Date

May 1, 2020

Last Update Submit

August 4, 2023

Conditions

COVIDThrombosisPulmonary EmbolismDeep Vein Thrombosis

Keywords

COVIDThrombosisVenous ThromboembolismPulmonary EmbolismDeep Vein ThrombosisLow Molecular Weight Heparin

Outcome Measures

Primary Outcomes (1)

  • Venous thromboembolism

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

    hospitalization stay (up to 28 days)

Secondary Outcomes (7)

  • Major bleeding

    hospitalization stay (up to 28 days)

  • Major Bleeding and Clinically Relevant Non-Major Bleeding

    hospitalization stay (up to 28 days)

  • Net Clinical Benefit

    hospitalization stay (up to 28 days) and 60 days

  • Venous Thromboembolism at other sites

    hospitalization stay (up to 28 days)

  • Arterial Thrombosis

    hospitalization stay (up to 28 days)

  • +2 more secondary outcomes

Study Arms (2)

Low Prophylactic Dose of Low Molecular Weight Heparin

ACTIVE COMPARATOR

Enoxaparin, Tinzaparin, Nadroparin, Dalteparin

Drug: Enoxaparin

Weight-Adjusted Prophylactic Dose Low Molecular Weight Heparin

EXPERIMENTAL

Enoxaparin, Tinzaparin, Nadroparin, Dalteparin

Drug: Enoxaparin

Interventions

EnoxaparinDRUG

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

Also known as: Tinzaparin, Nadroparin, Dalteparin
Weight-Adjusted Prophylactic Dose Low Molecular Weight Heparin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Amiens Academic Hospital

Amiens, France

Location

Besançon Academic Hospital

Besançon, France

Location

Brest Academic Hospital

Brest, France

Location

Civil Hospital

Colmar, France

Location

Dijon Academic Hospital

Dijon, France

Location

Kremlin Bicêtre Academic Hospital

Le Kremlin-Bicêtre, France

Location

Lille Academic Hospital

Lille, France

Location

Groupe Hospitalier Unéos

Metz, France

Location

Metz-Thionville Regional Hospital

Metz, France

Location

Montpellier Academic Hospital

Montpellier, France

Location

Emile Muller Hospital

Mulhouse, France

Location

Nancy Academic Hospital

Nancy, France

Location

George Pompidou European Hospital

Paris, France

Location

Lariboisière Academic Hospital

Paris, France

Location

St Etienne Academic Hospital

Saint-Etienne, France

Location

Strasbourg Academic Hospital

Strasbourg, France

Location

Toulouse Academic Hospital

Toulouse, France

Location

Related Publications (3)

  • 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.

    PMID: 37350990RESULT

  • 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. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

    PMID: 35244208DERIVED

  • 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.

    PMID: 33502773DERIVED

Related Links

MeSH Terms

Conditions

ThrombosisPulmonary EmbolismVenous ThrombosisVenous Thromboembolism

Interventions

EnoxaparinTinzaparinNadroparinDalteparin

Condition Hierarchy (Ancestors)

Embolism and ThrombosisVascular DiseasesCardiovascular DiseasesLung DiseasesRespiratory Tract DiseasesEmbolismThromboembolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-WeightHeparinGlycosaminoglycansPolysaccharidesCarbohydrates

Study Officials

  • El Mehdi Siaghy

    Research and Innovation Department, Nancy University Hospital

    STUDY DIRECTOR

  • Stéphane Zuily, MD, PhD

    Nancy Academic Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Multicenter randomized (1:1) controlled open-label trial, stratified on disease severity (admission to ICU or not)
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

May 1, 2020

First Posted

May 4, 2020

Study Start

May 13, 2020

Primary Completion

April 29, 2021

Study Completion

September 14, 2021

Last Updated

August 7, 2023

Record last verified: 2023-08

Data Sharing

IPD Sharing
Will not share

Locations

FR(17)