Pragmatic randomized clinical trial of patients admitted to the hospital with confirmed COVID-19 infection and elevated D-Dimer. Randomization 1:1 - Group 1 will undergo a routine full anticoagulation (oral or parenteral when needed) strategy; and group 2 will receive usual standard of care with prophylactic anticoagulation
Patients admitted to hospital with confirmed COVID-19, and who meet the eligibility criteria
will be invited to participate in the proposed study. Following the application of the
informed consent form, they will collect the D-dimer (if they have not yet collected it
routinely from the hospital) and confirm the value over the normal limit in patients with
confirmed COVID-19, will be randomized to 2 groups in the 1:1 ratio. Group 1 will follow the
strategy of routine use of full anticoagulation therapy (oral or parenteral when indicated);
and group 2 will follow the usual standard care with in-hospital prophylactic anticoagulation
(without routine full anticoagulation).
Drug: Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed
Routine full anticoagulation strategy
Drug: Group 2: control group with enoxaparin 40mg/d
Usual standard of care and currently have no indication of full anticoagulation.
Inclusion Criteria:
- Patients with confirmed diagnosis of COVID-19 admitted to hospital;
- Duration of symptoms related to hospitalization ≤ 14 days;
- Patients ≥ 18 year old;
- D-dimer above the upper limit of normal (collected until 72 hours before the
randomization);
- Agreement to participate by providing the informed consent form (ICF).
Exclusion Criteria:
- Patients with indication for full anticoagulation during inclusion (for example,
diagnosis of venous thromboembolism, atrial fibrillation, mechanical valve
prosthesis);
- Platelets < 50,000 /mm3
- Need for ASA therapy > 100 mg;
- Need for P2Y12 inhibitor therapy (clopidogrel, ticagrelor or prasugrel);
- Chronic use of non-hormonal anti-inflammatory drugs;
- Sustained uncontrolled systolic blood pressure (BP) of ≥180 mmHg or diastolic BP of
≥100 mmHg;
- INR > 1,5;
- Patients contraindicated to full anticoagulation (active bleeding, liver failure,
blood dyscrasia or prohibitive hemorrhage risk as evaluated by the investigator);
- Criteria for disseminated intravascular coagulation (DIC);
- A history of hemorrhagic stroke or any intracranial bleeding at any time in the past
or current intracranial neoplasm (benign or malignant), cerebral metastases,
arteriovenous (AV) malformation, or aneurysm;
- Active cancer (excluding non-melanoma skin cancer) defined as cancer not in remission
or requiring active chemotherapy or adjunctive therapies such as immunotherapy or
radiotherapy;
- Hypersensitivity to rivaroxaban;
- Use of strong inhibitors of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp)
(e.g. protease inhibitors, ketoconazole, Itraconazole) and/or use of P-gp and strong
CYP3A4 inducers (such as but not limited to rifampin/rifampicin, rifabutin,
rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's Wort);
- Known HIV infection;
- Creatinine clearance < 30 ml/min according to the Cockcroft-Gault Formula;
- Pregnancy or breastfeeding.
Centro de Estudos Clínicos do Hospital Cárdio Pulmonar
Salvador, Bahia, Brazil
Instituto de Ensino e Pesquisa do Hospital da Bahia
Salvador, Bahia, Brazil
Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
Salvador, Bahia, Brazil
Hospital Maternidade São Vicente de Paulo
Barbalha, Ceará, Brazil
Centro de Ensino e Aperfeiçoamento em Pesquisa - CEAP
Serra, Espirito Santo, Brazil
Centro de Pesquisas Cardiológicas de Goiânia do Hospital das Clínicas (UFG)
Goiânia, Goiás, Brazil
Hospital Vera Cruz
Belo Horizonte, Minas Gerais, Brazil
Núcleo de Ciências de Saúde - Unidade de Pesquisa - Hospital Felício Rocho
Belo Horizonte, Minas Gerais, Brazil
Centro de Pesquisa Clínica do Hospital de Clínicas da Universidade Federal de Uberlândia
Uberlândia, Minas Gerais, Brazil
Hospital Universitário da Universidade Estadual de Londrina
Londrina, Paraná, Brazil
Hospital Agamenon Magalhães
Recife, Pernambuco, Brazil
Real Hospital Português de Beneficência em Pernambuco
Recife, Pernambuco, Brazil
Hospital Moinhos de Vento
Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Nereu Ramos
Florianópolis, Santa Catarina, Brazil
Instituto Baia Sul de Ensino E Pesquisa Dr. Irineu May Brodbeck / Hospital Baía Sul
Florianópolis, Santa Catarina, Brazil
Hospital Regional Hans Dieter Schmidt
Joinville, Santa Catarina, Brazil
Hospital de Amor de Barretos - (Pio XII)
Barretos, São Paulo, Brazil
Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - Unesp
Botucatu, São Paulo, Brazil
Hospital Universitário São Francisco de Assis
Bragança Paulista, São Paulo, Brazil
Hospital Regional do Litoral Norte
Caraguatatuba, São Paulo, Brazil
Hospital Regional de Registro
Registro, São Paulo, Brazil
Praxis Pesquisa Médica
Santo André, São Paulo, Brazil
Centro Integrado de Pesquisa (CIP) - Hospital de Base de Rio Preto
São José Do Rio Preto, São Paulo, Brazil
Hospital Regional de São José dos Campos
São José Dos Campos, São Paulo, Brazil
Santa Casa de Misericórdia de Votuporanga
Votuporanga, São Paulo, Brazil
Hospital Naval Marcílio Dias
Rio de Janeiro, Brazil
BP - A Beneficência Portuguesa de São Paulo
São Paulo, Brazil
Hcor - Hospital do Coração
São Paulo, Brazil
Hospital Israelita Albert Einstein
São Paulo, Brazil
Hospital Moriah
São Paulo, Brazil
Hospital Samaritano Paulista
São Paulo, Brazil
Hospital Santa Paula
São Paulo, Brazil
Hospital São Paulo
São Paulo, Brazil
Instituto Dante Pazzanese de Cardiologia
São Paulo, Brazil
Instituto de Assistência Médica ao Servidor Público Estadual de S. Paulo
São Paulo, Brazil
Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP-InCor-HCFMUSP
São Paulo, Brazil
Renato D. Lopes, MD, PhD, Study Chair
BCRI