Thromboprophylaxis for Patients in ICU With COVID-19

NCT ID: NCT04623177

Last Updated: 2022-03-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

822 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-01

Study Completion Date

2020-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Covid19 Anticoagulant Therapy Thrombosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

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 interventions assigned to this group

No heparin

Patients receiving no anticoagulant drug within the first 48 hours after the ICU admission

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Universitario Doctor Peset

OTHER

Sponsor Role collaborator

Hospital Clinic of Barcelona

OTHER

Sponsor Role collaborator

Hospital Universitario La Paz

OTHER

Sponsor Role collaborator

Hospital Universitario La Fe

OTHER

Sponsor Role collaborator

Hospital de Sant Joan Despí Moisès Broggi

OTHER

Sponsor Role collaborator

University of Navarrra Hospital (Clinica Universitaria)

OTHER

Sponsor Role collaborator

Hospital de Cruces

OTHER

Sponsor Role collaborator

Instituto de Investigacion Sanitaria La Fe

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raquel Ferrandis, MD

Role: STUDY_CHAIR

Hospital Universitario La Fe

Locations

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Hospital Clínico Universitario Lozano Blesa

Zaragoza, Aragon, Spain

Site Status

Hospital Universitario de Araba

Álava, Basque Country, Spain

Site Status

Complejo Asistencial Universitario de León

León, Castille and León, Spain

Site Status

Hospital Universitario Rio Ortega

Valladolid, Castille and León, Spain

Site Status

Hospital General de Ciudad Real

Ciudad Real, Castille-La Mancha, Spain

Site Status

Hospital Clinic Barcelona

Barcelona, Catalonia, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, Spain

Site Status

Hospital de Terrasa

Barcelona, Catalonia, Spain

Site Status

Complejo Hospitalario de Cáceres

Cáceres, Extramedura, Spain

Site Status

Hospital Unversitario A Coruña

A Coruña, Galicia, Spain

Site Status

Complexo Hospitalario Universitario de Ferrol

A Coruña, Galicia, Spain

Site Status

Complexo Hospitalario Universitario de Pontevedra

Pontevedra, Galicia, Spain

Site Status

Hospital Povisa

Pontevedra, Galicia, Spain

Site Status

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas, Gran Canaria, Spain

Site Status

Hospital Universitario Severo Ochoa

Leganés, Madrid, Spain

Site Status

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital General Universitario de Alicante

Alicante, Valencia, Spain

Site Status

Hospital Universitario San Juan de Alicante

Alicante, Valencia, Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Sanitas Cima

Barcelona, , Spain

Site Status

Hospital Sant Joan Despí

Barcelona, , Spain

Site Status

Hospital Universitario La Princesa

Madrid, , Spain

Site Status

Hospital Universitario Infanta Leonor

Madrid, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Infanta Sofia

Madrid, , Spain

Site Status

Hospital Rafael Méndez

Murcia, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Arnau de Vilanova

Valencia, , Spain

Site Status

Hospital Universitario Doctor Peset

Valencia, , Spain

Site Status

Hospital Universitari La Fe

Valencia, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 32311448 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32109013 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30642917 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32527286 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32591185 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32387623 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32171076 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32619329 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32220112 (View on PubMed)

Other Identifiers

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RegCoVid-19

Identifier Type: -

Identifier Source: org_study_id

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