Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec:242:115-122.
doi: 10.1016/j.ahj.2021.08.016. Epub 2021 Sep 1.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial

Eduardo Ramacciotti  1 , Leandro Barile Agati  2 , Daniela Calderaro  3 , Giuliano Giova Volpiani  4 , Caroline Candida Carvalho de Oliveira  4 , Valéria Cristina Resende Aguiar  4 , Elizabeth Rodrigues  2 , Marcone Lima Sobreira  5 , Edwaldo Edner Joviliano  6 , Cesar Dusilek  7 , Kenji Itinose  7 , Rogério Aparecido Dedivitis  8 , André Sementilli Cortina  8 , Suzanna Maria Viana Sanches  9 , Nara Franzin de Moraes  10 , Paulo Fernando Guimarães Morando Marzocchi Tierno  10 , André Luiz Malavasi Longo de Oliveira  11 , Adriano Tachibana  12 , Rodrigo Caruso Chate  12 , Marcus Vinícius Barbosa Santos  13 , Bruno Bezerra de Menezes Cavalcante  14 , Ricardo Cesar Rocha Moreira  15 , Chang Chiann  16 , Alfonso Tafur  17 , Alex C Spyropoulos  18 , Renato D Lopes  19
Affiliations

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial

Eduardo Ramacciotti et al. Am Heart J. 2021 Dec.

Abstract

Background: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis.

Design: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria.

Summary: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest ER: Research support from Bayer, Pfizer, Bristol-Myers Squibb, Brazilian Ministry of Science and Technology. Consulting fees from Bayer, Daiichi-Sankyo, Aspen Pharma, Biomm Pharma, and Pfizer. DC: Research support from Stago. Consulting fees from Bayer and Janssen. AT: Idorsia, Janssen, Bristol-Myers Squibb, Novo Nordisk, research support. Janssen, Recovery force, educational funding. ACS: Janssen, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, Portola, ATLAS Group: Consultancy; Janssen, Boehringer-Ingelheim: Research Funding. RDL: Research support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer; Consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola.

Figures

Figure 1
Figure 1
The MICHELLE Trial design. CTPA, computed tomography pulmonary angiogram; IMPROVED, modified International Medical Prevention Registry on Venous Thromboembolism; R, randomization; VTE, venous thromboembolism.
Figure 2
Figure 2
The MICHELLE Trial visit schedule. CTPA, computed tomography pulmonary angiogram.
See this image and copyright information in PMC

References

    1. Bikdeli B, Madhavan MV, Jimenez D, et al. 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;75:2950–2973. doi: 10.1016/j.jacc.2020.04.031. (In eng) - DOI - PMC - PubMed
    1. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383:120–128. doi: 10.1056/NEJMoa2015432. (In eng) - DOI - PMC - PubMed
    1. Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46:1089–1098. doi: 10.1007/s00134-020-06062-x. (In eng) - DOI - PMC - PubMed
    1. Piazza G, Campia U, Hurwitz S, et al. Registry of arterial and venous thromboembolic complications in patients with COVID-19. J Am Coll Cardiol. 2020;76:2060–2072. doi: 10.1016/j.jacc.2020.08.070. (In eng) - DOI - PMC - PubMed
    1. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145–147. doi: 10.1016/j.thromres.2020.04.013. (In eng) - DOI - PMC - PubMed

Publication types

MeSH terms