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Covid19NCT04623177

Thromboprophylaxis for Patients in ICU With COVID-19

An observational study of Covid19 and Anticoagulant Therapy, run by Instituto de Investigacion Sanitaria La Fe at 31 sites in Spain.

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

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19, Anticoagulant Therapy, Thrombosis
How many people
822 participants
Where
31 sitesSpain
Study dates
1 Mar 2020to 30 Nov 2020
Phase
Observational
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

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

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

Spain31 sites

  • Hospital Unversitario A Coruña

    A Coruña, Galicia, 15006

  • Complexo Hospitalario Universitario de Ferrol

    A Coruña, Galicia, 15405

  • Hospital Universitario de Araba

    Álava, Basque Country, 1009

  • Hospital General Universitario de Alicante

    Alicante, Valencia, 3010

  • Hospital Universitario San Juan de Alicante

    Alicante, Valencia, 3550

  • Hospital Clinic Barcelona

    Barcelona, Catalonia, 08036

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, Catalonia, 8041

  • Hospital de Terrasa

    Barcelona, Catalonia, 8227

  • Hospital del Mar

    Barcelona, 8003

  • Hospital Sanitas Cima

    Barcelona, 8034

  • Hospital Sant Joan Despí

    Barcelona, 8970

  • Complejo Hospitalario de Cáceres

    Cáceres, Extramedura, 10003

  • Hospital General de Ciudad Real

    Ciudad Real, Castille-La Mancha, 13005

  • Hospital Universitario de Gran Canaria Dr. Negrín

    Las Palmas, Gran Canaria, 35010

  • Hospital Universitario Severo Ochoa

    Leganés, Madrid, 28911

  • Complejo Asistencial Universitario de León

    León, Castille and León, 24080

  • Hospital Universitario La Princesa

    Madrid, 28006

  • Hospital Universitario Infanta Leonor

    Madrid, 28031

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Infanta Sofia

    Madrid, 28702

  • Hospital Rafael Méndez

    Murcia, 30817

  • Clínica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Complexo Hospitalario Universitario de Pontevedra

    Pontevedra, Galicia, 36071

  • Hospital Povisa

    Pontevedra, Galicia, 36211

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Arnau de Vilanova

    Valencia, 46015

  • Hospital Universitario Doctor Peset

    Valencia, 46017

  • Hospital Universitari La Fe

    Valencia, 46026

  • Hospital Universitario Rio Ortega

    Valladolid, Castille and León, 47012

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, Aragon, 50009

Other trials in Spain

About this study

Official title: 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.

Read the 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.

Keywords
Covid19, Low Molecular weight heparin, Thromboprophylaxis, Anticoagulant treatment, Thrombosis
Medical subject headings
COVID-19, Thrombosis

What participants receive

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

Study groups in NCT04623177
Study groupRoleWhat they receive
AnticoagulationPatients receiving an anticoagulant dose (equal or higher than 150 IU/kg/24 h) of LMWH within the first 48 hours after the ICU admission
ThromboprophylaxisPatients receiving a prophylactic dose (lower than 150 IU/kg/24 h) of LMWH within the first 48 hours after the ICU admission
No heparinPatients receiving no anticoagulant drug within the first 48 hours after the ICU admission

What is being measured

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

  1. ICU mortality

    Rate of mortality

    Measured: From admission to ICU discharge, an average of 1 month

Secondary outcomes (5)

  1. ICU incidence of thrombotic events

    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

    Measured: From admission to ICU discharge, an average of 1 month

  2. ICU incidence of bleeding events

    Composite endpoint to evaluate safety made up of: bleeding needing transfusion, bleeding wit hemodynamic repercussion, other bleeding (minor bleeding)

    Measured: From admission to ICU discharge, an average of 1 month

  3. Length of ICU stay

    Days admitted in ICU

    Measured: From admission to ICU discharge, an average of 1 month

  4. Length of invasive mechanical ventilation

    Days treated with invasive mechanical ventilation (controlled or assisted)

    Measured: From admission to ICU discharge, an average of 1 month

  5. Effect of LMWH in other parameters

    Description of the relationship if any between the use of LMWH and thrombotic or inflammatory parameters (D-Dimer levels, ferritin) or lung dead space

    Measured: From admission to ICU discharge, an average of 1 month

Timeline

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

  1. First posted10 Nov 2020
  2. Study start1 Mar 2020
  3. Primary completion30 Sep 2020
  4. Study completion30 Nov 2020

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
822 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04623177
Sponsor's protocol ID
RegCoVid-19
Status last verified
Oct 2020
First submitted
2 Nov 2020
Last updated
31 Mar 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian C, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quere I, Dimakakos EP, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Burton JR, Francese DP, Wang EY, Falanga A, McLintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Monreal M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Jun 16;75(23):2950-2973. doi: 10.1016/j.jacc.2020.04.031. Epub 2020 Apr 17.

    PubMed 32311448

  • Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

    PubMed 32109013

  • Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019 Feb 28;133(9):906-918. doi: 10.1182/blood-2018-11-882993. Epub 2019 Jan 14.

    PubMed 30642917

  • Ferrandis R, Llau JV, Quintana M, Sierra P, Hidalgo F, Cassinello C, Gomez-Luque A. COVID-19: opening a new paradigm in thromboprophylaxis for critically ill patients? Crit Care. 2020 Jun 11;24(1):332. doi: 10.1186/s13054-020-03052-9. No abstract available.

    PubMed 32527286

  • Llau JV, Ferrandis R, Sierra P, Hidalgo F, Cassinello C, Gomez-Luque A, Quintana M, Amezaga R, Gero M, Serrano A, Marcos P. SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection. Rev Esp Anestesiol Reanim (Engl Ed). 2020 Aug-Sep;67(7):391-399. doi: 10.1016/j.redar.2020.05.007. Epub 2020 May 23.

    PubMed 32591185

  • Paranjpe I, Fuster V, Lala A, Russak AJ, Glicksberg BS, Levin MA, Charney AW, Narula J, Fayad ZA, Bagiella E, Zhao S, Nadkarni GN. Association of Treatment Dose Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19. J Am Coll Cardiol. 2020 Jul 7;76(1):122-124. doi: 10.1016/j.jacc.2020.05.001. Epub 2020 May 6. No abstract available.

    PubMed 32387623

  • 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

  • Tang N, Bai H, Xiong D, Sun Z. Specific coagulation markers may provide more therapeutic targets in COVID-19 patients receiving prophylactic anticoagulant. J Thromb Haemost. 2020 Sep;18(9):2428-2430. doi: 10.1111/jth.14988. No abstract available.

    PubMed 32619329

  • 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

Questions about this trial

What is this clinical trial studying?

An observational study of Covid19 and Anticoagulant Therapy, run by Instituto de Investigacion Sanitaria La Fe at 31 sites in Spain.

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 4 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 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Spain. 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.

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?

ICU mortality (time frame: From admission to ICU discharge, an average of 1 month). 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 NCT04623177, which also lists 9 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 31 Mar 2022.

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