Thromboprophylaxis for Patients in ICU With COVID-19

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04623177
• Other study ID #: RegCoVid-19
• Status: Completed
• Start date: March 1, 2020
• Est. completion date: November 30, 2020

Study information

• Verified date: October 2020
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 822
• Est. completion date: November 30, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anticoagulant Therapy
• COVID-19
• Covid19
• Thrombosis

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Universitario de Ferrol	A Coruña	Galicia
Spain	Hospital Unversitario A Coruña	A Coruña	Galicia
Spain	Hospital Universitario de Araba	Álava	País Vasco
Spain	Hospital General Universitario de Alicante	Alicante	Comunidad Valenciana
Spain	Hospital Universitario San Juan de Alicante	Alicante	Comunidad Valenciana
Spain	Hospital Clinic Barcelona	Barcelona	Cataluña
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital de Terrasa	Barcelona	Cataluña
Spain	Hospital del Mar	Barcelona
Spain	Hospital Sanitas Cima	Barcelona
Spain	Hospital Sant Joan Despí	Barcelona
Spain	Complejo Hospitalario de Cáceres	Cáceres	Extramedura
Spain	Hospital General de Ciudad Real	Ciudad Real	Castilla La Mancha
Spain	Hospital Universitario de Gran Canaria Dr. Negrín	Las Palmas	Gran Canaria
Spain	Hospital Universitario Severo Ochoa	Leganés	Madrid
Spain	Complejo Asistencial Universitario de León	León	Castilla Y León
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Infanta Sofia	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Rafael Méndez	Murcia
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Complexo Hospitalario Universitario de Pontevedra	Pontevedra	Galicia
Spain	Hospital Povisa	Pontevedra	Galicia
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitari La Fe	Valencia
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital Universitario Rio Ortega	Valladolid	Castilla Y León
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza	Aragón

Sponsors (8)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe	Hospital Clinic of Barcelona, Hospital de Sant Joan Despí Moisès Broggi, Hospital Universitario Cruces, Hospital Universitario Doctor Peset, Hospital Universitario La Fe, Hospital Universitario La Paz, University of Navarrra Hospital (Clinica Universitaria)

Country where clinical trial is conducted

Spain, 

References & Publications (9)

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, Quéré 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. Review. — View Citation

Ferrandis R, Llau JV, Quintana M, Sierra P, Hidalgo F, Cassinello C, Gómez-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. — View Citation

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. — View Citation

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. Review. — View Citation

Llau JV, Ferrandis R, Sierra P, Hidalgo F, Cassinello C, Gómez-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. English, Spanish. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ICU mortality	Rate of mortality	From admission to ICU discharge, an average of 1 month
Secondary	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	From admission to ICU discharge, an average of 1 month
Secondary	ICU incidence of bleeding events	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
Secondary	Length of ICU stay	Days admitted in ICU	From admission to ICU discharge, an average of 1 month
Secondary	Length of invasive mechanical ventilation	Days treated with invasive mechanical ventilation (controlled or assisted)	From admission to ICU discharge, an average of 1 month
Secondary	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	From admission to ICU discharge, an average of 1 month