Thromboprophylaxis for Patients in ICU With COVID-19

March 29, 2022 updated by: Instituto de Investigacion Sanitaria La Fe

Effectiveness of Thromboprophylaxis With Low Molecular Weight Heparin in Critically Ill Patients With COVID-19. A Prospective, Cohort, Multicenter Study.

The respiratory distress that goes with COVID-19 infection has been related to a procoagulant state, with thrombosis at both venous and arterial levels, that determines hypoxia and tissue dysfunction at several organs. The main sign of this thrombotic activity seems to be the D-Dimers, that have been proposed to identify patients with poor prognosis at an early stage.

Knowledge on how to prevent or even treat this procoagulant state is scarce. COVID-19 patients may be out of general thromboprophylaxis recommendations, and recent studies suggest a better prognosis in severe COVID-19 patients receiving anticoagulant therapy with low molecular weight heparin (LMWH). However, the LMWH efficacy and safety, mainly in patients admitted to an Intensive Care Unit, remains to be validated.

Study Overview

Status

Completed

Conditions

Detailed Description

Many reports have postulated a procoagulant state along with the respiratory distress caused by coronavirus SARS-CoV2. A complex physiopathology has been proposed trying to explain this profile, mainly based on the thromboinflammatory concept, with thrombosis at both venous and arterial levels. Microvascular thrombi impair the blood flow all over the body, with a vascular shunt due to capillary obstruction, that determines hypoxia and tissue dysfunction at several organs, being the lung the more affected one.

Although D-Dimers (DD) are not specific indicators of clot formation, its elevation, in combination with other parameters (hyperfibrinogenemia, mild thrombocytopenia) may suggest a systemic coagulation activation with an increase of thrombin generation and fibrinolysis. In fact, in a retrospective Chinese analysis, a DD higher than 1000 ng/ml was proposed to identify patients with poor prognosis at an early stage.

Nevertheless, knowledge on how to prevent or even treat this procoagulant state is scarce. Thromboprophylaxis with low molecular-weight heparin (LMWH) is recommended in most medical patients admitted to the hospital and in nearly all patients in an Intensive Care Unit (ICU). But COVID-19 patients may be out of these recommendations, and some treatment schemes has been proposed, although how to decide the suitable LMWH for each clinical situation is controversial. Recent retrospective studies suggest a better prognosis in severe COVID-19 patients receiving anticoagulant therapy with LMWH. However, the LMWH efficacy and safety, mainly in COVID-19 patients admitted to the ICU, remains to be validated.

Study Type

Observational

Enrollment (Actual)

822

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

  • Spain
      • Barcelona, Spain, 8003
        • Hospital del Mar
      • Barcelona, Spain, 8034
        • Hospital Sanitas CIMA
      • Barcelona, Spain, 8970
        • Hospital Sant Joan Despí
      • Madrid, Spain, 28006
        • Hospital Universitario La Princesa
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28031
        • Hospital Universitario Infanta Leonor
      • Madrid, Spain, 28702
        • Hospital Universitario Infanta Sofia
      • Murcia, Spain, 30817
        • Hospital Rafael Méndez
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46015
        • Hospital Arnau de Vilanova
      • Valencia, Spain, 46017
        • Hospital Universitario Doctor Peset
      • Valencia, Spain, 46026
        • Hospital Universitari La Fe
    • Aragón
      • Zaragoza, Aragón, Spain, 50009
        • Hospital Clínico Universitario Lozano Blesa
    • Castilla La Mancha
      • Ciudad Real, Castilla La Mancha, Spain, 13005
        • Hospital General de Ciudad Real
    • Castilla Y León
      • León, Castilla Y León, Spain, 24080
        • Complejo Asistencial Universitario de Leon
      • Valladolid, Castilla Y León, Spain, 47012
        • Hospital Universitario Río Ortega
    • Cataluña
      • Barcelona, Cataluña, Spain, 08036
        • Hospital Clinic Barcelona
      • Barcelona, Cataluña, Spain, 8041
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Cataluña, Spain, 8227
        • Hospital de Terrasa
    • Comunidad Valenciana
      • Alicante, Comunidad Valenciana, Spain, 3010
        • Hospital General Universitario de Alicante
      • Alicante, Comunidad Valenciana, Spain, 3550
        • Hospital Universitario San Juan de Alicante
    • Extramedura
      • Cáceres, Extramedura, Spain, 10003
        • Complejo Hospitalario de Cáceres
    • Galicia
      • A Coruña, Galicia, Spain, 15006
        • Hospital Unversitario A Coruña
      • A Coruña, Galicia, Spain, 15405
        • Complexo Hospitalario Universitario de Ferrol
      • Pontevedra, Galicia, Spain, 36071
        • Complexo Hospitalario Universitario de Pontevedra
      • Pontevedra, Galicia, Spain, 36211
        • Hospital Povisa
    • Gran Canaria
      • Las Palmas, Gran Canaria, Spain, 35010
        • Hospital Universitario de Gran Canaria Dr. Negrin
    • Madrid
      • Leganés, Madrid, Spain, 28911
        • Hospital Universitario Severo Ochoa
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad de Navarra
    • País Vasco
      • Álava, País Vasco, Spain, 1009
        • Hospital Universitario de Araba

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All consecutive COVID-19 patients admitted to participating ICUs from March 12th to September 1st were included if they fulfill the inclusion criteria and present no exclusion criteria

Description

Inclusion Criteria:

  • Confirmed SARS-CoV2 infection from a respiratory tract sample using a polymerase chain reaction assay.
  • Admitted to ICU

Exclusion Criteria:

  • Non-confirmed SARS-CoV2 infection
  • No data at first day ICU admission
  • Patient with do-not resuscitate orders
  • Patient who did not meet the outcomes of death or ICU discharge by the time of study completion date

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

Cohorts and Interventions

Group / Cohort
Anticoagulation
Patients receiving an anticoagulant dose (equal or higher than 150 IU/kg/24 h) of LMWH within the first 48 hours after the ICU admission
Thromboprophylaxis
Patients receiving a prophylactic dose (lower than 150 IU/kg/24 h) of LMWH within the first 48 hours after the ICU admission
No heparin
Patients receiving no anticoagulant drug within the first 48 hours after the ICU admission

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ICU mortality
Time Frame: From admission to ICU discharge, an average of 1 month
Rate of mortality
From admission to ICU discharge, an average of 1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ICU incidence of thrombotic events
Time Frame: From admission to ICU discharge, an average of 1 month
A composite endpoint to evaluate efficacy made up of: myocardial infarction, stroke, incidental pulmonary thromboembolism, pulmonary thromboembolism with worsening of hypoxemia, Pulmonary thromboembolism with hemodynamic repercussion, other venous thromboses without pulmonary thromboembolism
From admission to ICU discharge, an average of 1 month
ICU incidence of bleeding events
Time Frame: From admission to ICU discharge, an average of 1 month
Composite endpoint to evaluate safety made up of: bleeding needing transfusion, bleeding wit hemodynamic repercussion, other bleeding (minor bleeding)
From admission to ICU discharge, an average of 1 month
Length of ICU stay
Time Frame: From admission to ICU discharge, an average of 1 month
Days admitted in ICU
From admission to ICU discharge, an average of 1 month
Length of invasive mechanical ventilation
Time Frame: From admission to ICU discharge, an average of 1 month
Days treated with invasive mechanical ventilation (controlled or assisted)
From admission to ICU discharge, an average of 1 month
Effect of LMWH in other parameters
Time Frame: From admission to ICU discharge, an average of 1 month
Description of the relationship if any between the use of LMWH and thrombotic or inflammatory parameters (D-Dimer levels, ferritin) or lung dead space
From admission to ICU discharge, an average of 1 month

Collaborators and Investigators

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

Sponsor

Instituto de Investigacion Sanitaria La Fe

Collaborators

Hospital Clinic of Barcelona
Hospital Universitario La Fe
Hospital Universitario La Paz
Hospital de Sant Joan Despí Moisès Broggi
Hospital Universitario Doctor Peset
Hospital Universitario Cruces
University of Navarrra Hospital (Clinica Universitaria)

Investigators

  • Study Chair: Raquel Ferrandis, MD, Hospital Universitario la Fe

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)

March 1, 2020

Primary Completion (Actual)

September 30, 2020

Study Completion (Actual)

November 30, 2020

Study Registration Dates

First Submitted

November 2, 2020

First Submitted That Met QC Criteria

November 9, 2020

First Posted (Actual)

November 10, 2020

Study Record Updates

Last Update Posted (Actual)

March 31, 2022

Last Update Submitted That Met QC Criteria

March 29, 2022

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RegCoVid-19

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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