COVID-19 Antithrombotic Rivaroxaban Evaluation

NCT04757857 | Terminated Phase 4 DMC

• 1 other identifier: 36066320.5.1001.0070
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 36

Brief Summary

There are several ways in which the COVID-19 pandemic may affect the prevention and management of thrombotic and thromboembolic disease, either direct effect or the indirect effects of infection, such as through severe illness and hypoxia, may predispose patients to thrombotic events. The severe inflammatory response, critical illness, and underlying traditional risk factors may all predispose to thrombotic events. Therefore, considering the high-risk profile of cardiovascular comorbidities in patients with COVID-19, it is scientifically relevant to evaluate the use of anticoagulants as an adjunctive treatment in the context of COVID-19. Indeed, it will be tested the hypothesis that the use of moderate dose of rivaroxaban has a beneficial effect in the treatment of patients with a confirmed or probable diagnosis of COVID-19 infection, with no clear indication for hospitalization (mild and moderate cases) upon initial medical care, by reducing the need of hospitalization due to complications related to COVID-19.

Conditions

COVID-19

Keywords

SARS-Cov-2; COVID-19; Rivaroxaban; Antithrombotic

Outcome Measures

Primary Outcomes (4)

• Venous thromboembolic events (VTE)

  Defined as deep venous thrombosis, acute pulmonary embolism, other major venous thrombotic events.

  Within 30 days from randomization

• Mechanical ventilation free-survival

  Defined as survival without requirement of mechanical ventilation.

  Within 30 days from randomization

• Major Adverse Cardiovascular Events (MACE)

  Defined as acute myocardial infarction, stroke or acute limb ischemia

  Within 30 days from randomization

• Out-of-hospital death not attributed to major injury

  Death that occurred out of hospital due to any cause not related to trauma or other major injury

  Within 30 days from randomization

Secondary Outcomes (9)

• Time from randomization to hospitalization

  30 days from randomization

• Length of Hospitalization

  30 days from randomization

• Hospitalization in Intensive Care Unit

  30 days from randomization

• Clinical requirement of mechanical ventilation

  30 days from randomization

• Clinical duration of mechanical ventilation

  30 days from randomization

Study Arms (2)

Rivaroxaban 10 mg

ACTIVE COMPARATOR

Participants will receive, from the 1st to the 14th day, a dose of 10 mg of rivaroxaban - OA (Oral Administration).

Drug: Rivaroxaban 10 mg

Best locally standardized care

NO INTERVENTION

According to the study protocol, participating investigators are advised to follow the best available local practice in each participating site. There is no formal recommendation for any particular COVID-19 treatment, except symptomatic therapies.

Interventions

Rivaroxaban 10 mg DRUG

Rivaroxaban pharmaceutical form will be tablets of 10 mg

Also known as: Xarelto

Rivaroxaban 10 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years old;
• Evaluated in the emergency unit with probable or confirmed infection by COVID-19;
• Present mild or moderate signs and symptoms, with no clear indication for hospitalization;
• Present at least 2 risk factors for complication:
• years
• Hypertension
• Diabetes mellitus
• Asthma
• Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases
• Smoking
• Immunosuppression
• Obesity (BMI\> 30)
• History of non-active cancer
• Bed restriction or reduced mobility (≥50% of the wake time without walking)
• Previous history of VTE

You may not qualify if:

• Patients \<18 years old;
• Hospitalization indication upon first medical care;
• Positive test for influenza in the first visit;
• Any known liver disease associated with coagulopathy; INR (International Normalized Ratio) \> 1.5;
• Pregnant, lactating or with the possibility of becoming pregnant and without using an adequate contraceptive method;
• High risk of bleeding; History of bronchiectasis or pulmonary cavitation, Significant bleeding in the last 3 months, Active gastroduodenal ulcer, history of recent bleeding (within 3 months) or a high risk of bleeding;
• Stroke within 1 month or any history of hemorrhagic or lacunar stroke or any intracranial bleeding or any intracranial neoplasia, brain metastasis, arteriovenous malformation or brain aneurysm;
• Severe heart failure with left ventricular ejection fraction \<30% (echocardiogram or other validated method previously documented) or symptoms of heart failure class III or IV of the New York Heart Association (NYHA);
• Estimated glomerular filtration rate (eGFR) \<30 mL / min;
• Clinical indication for dual antiplatelet therapy or anticoagulation therapy (VTE, atrial fibrillation / flutter, mechanical valve prosthesis);
• Marked thrombocytopenia (platelets \<50,000 / mm3);
• Non-cardiovascular disease that is associated with a poor prognosis, for example, active cancer (excluding non-melanoma skin cancer) defined as cancer without remission or requiring active chemotherapy or adjuvant therapies such as immunotherapy or radiation therapy or that increases the risk of an adverse reaction to the evaluated interventions;
• History of hypersensitivity or known contraindication to rivaroxaban;
• Systemic treatment with strong inhibitors of Cytochrome P450 3A4 (CYP3A4) and glycoprotein p (Pgp) (for example, systemic azole antimycotics, such as ketoconazole and human immunodeficiency virus \[HIV\] protein inhibitors, such as ritonavir) or strong inducers of CYP 3A4, that is, rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine;
• Current treatment being tested;

Sponsors & Collaborators

• Hospital Alemão Oswaldo Cruz: lead
• Bayer: collaborator
• Hospital Israelita Albert Einstein: collaborator
• Hospital do Coracao: collaborator
• Hospital Sirio-Libanes: collaborator
• Hospital Moinhos de Vento: collaborator
• Brazilian Research In Intensive Care Network: collaborator
• Brazilian Clinical Research Institute: collaborator

Study Sites (36)

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Location

Clínica Senhor do Bonfim

Feira de Santana, Estado de Bahia, Brazil

Location

Hospital de Base do Distrito Federal

Brasília, Federal District, Brazil

Location

Hospital de Campanha Covid-19 Goiânia/Sesgo

Goiânia, Goiás, Brazil

Location

Hospital Estadual de Urgências de Trindade/SESGO

Trindade, Goiás, Brazil

Location

Núcleo de Pesquisa Clínica do Hospital Vera Cruz

Belo Horizonte, Minas Gerais, 30190-130, Brazil

Location

Hospital São Lucas

Belo Horizonte, Minas Gerais, Brazil

Location

Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, Brazil

Location

Hospital Universitário Regional de Maringá

Maringá, Paraná, Brazil

Location

Beneficencia Nipo Brasileira Da Amazonia

Belém, Pará, 66060-575, Brazil

Location

Hospital Adventista de Belém

Belém, Pará, 66093-904, Brazil

Location

Associação Dr. Bartholomeu Tacchini

Bento Gonçalves, Rio Grande do Sul, Brazil

Location

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

Hospital das Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital Universitario de Santa Maria

Santa Maria, Rio Grande do Sul, 97900015, Brazil

Location

Clínica Procárdio Ltda

Blumenau, Santa Catarina, Brazil

Location

H&W Cardiologia LTDA

Joinville, Santa Catarina, 89204-250, Brazil

Location

Irmandade santa Casa de Araras

Araras, São Paulo, 13600-655, Brazil

Location

Alphacor Cardiologia Clínica e Diagnóstica LTDA

Barueri, São Paulo, Brazil

Location

Maestri e Kormann Consultoria Medico-Cientifica LTDA - EPP

Blumenau, São Paulo, Brazil

Location

Hospital Regional do Litoral Norte - Instituto Sócrates Guanaes

Caraguatatuba, São Paulo, Brazil

Location

Hospital Santos Dumont Litoral Norte

Caraguatatuba, São Paulo, Brazil

Location

Hospital de Corderiopolis

Cordeirópolis, São Paulo, Brazil

Location

Hospital Regional Jorge Rossman - Instituto Sócrates Guanaes

Itanhaém, São Paulo, Brazil

Location

Hospital Carlos Fernando Malzoni

Matão, São Paulo, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, São Paulo, 90035-001, Brazil

Location

Hospital Regional de Registro - Instituto Sócrates Guanaes

Registro, São Paulo, Brazil

Location

Hospital Unimed Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Location

Kaiser Clinica e Hospital Dia

São José do Rio Preto, São Paulo, 15015-110, Brazil

Location

Braile Hospital Dia Ltda

São José do Rio Preto, São Paulo, Brazil

Location

Hospital Policlin

São José dos Campos, São Paulo, 12 243 000, Brazil

Location

Hospital Regional de São José dos Campos - Instituto Sócrates Guanaes

São José dos Campos, São Paulo, Brazil

Location

Santa Casa de Misericórdia de Votuporanga

Votuporanga, São Paulo, Brazil

Location

International Research Center - Hospital Alemão Oswaldo Cruz

São Paulo, 01323-903, Brazil

Location

Hospital Leforte Liberdade

São Paulo, 01506-000, Brazil

Location

Incor - Instituto do Coração do Hospital das Clínicas da FMUSP

São Paulo, 05403-010, Brazil

Location

Related Publications (3)

• Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.

  PMID: 37591523 DERIVED

• Avezum A, Oliveira Junior HA, Neves PDMM, Alves LBO, Cavalcanti AB, Rosa RG, Veiga VC, Azevedo LCP, Zimmermann SL, Silvestre OM, Seabra Prudente RC, Morales Kormann AP, Moreira FR, Boszczowski I, de Brito Sobrinho E, da Silva E Souza A, Seligman R, de Souza Paolino B, Razuk A, Diogenes de Magalhaes Feitosa A, Monteiro Belmonte PL, Freitas das Neves Goncalves P, Hernandes ME, Fagundes AL, Sarmet Esteves JM, Tognon AP, Eikelboom J, Berwanger O, Lopes RD, Oliveira GBF; Coalition VIII COVID-19 Brazil Investigators. Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE - COALITION VIII randomised clinical trial. EClinicalMedicine. 2023 Jun;60:102004. doi: 10.1016/j.eclinm.2023.102004. Epub 2023 May 18.

  PMID: 37223666 DERIVED

• Oliveira GBF, Neves PDMM, Oliveira HA, Catarino DGM, Alves LBO, Cavalcanti AB, Rosa RG, Veiga VC, Azevedo LCP, Berwanger O, Lopes RD, Avezum A. Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII). Arq Bras Cardiol. 2023 Mar;120(3):e20220431. doi: 10.36660/abc.20220431. English, Portuguese.

  PMID: 37018790 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Álvaro Avezum, Ph.D

  International Research Center - Hospital Alemão Oswaldo Cruz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Manager - International Research Center

Model Details: Pragmatic, open-label, controlled randomized trial

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 17, 2021
• Study Start: September 29, 2020
• Primary Completion: August 8, 2022
• Study Completion: August 30, 2022
• Last Updated: January 25, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (36)