Full Anticoagulation Versus Prophylaxis in COVID-19: COALIZAO ACTION Trial

Phase 4

Completed

• Conditions: Coronavirus Infection

• Registration Number: NCT04394377
• Lead Sponsor: Brazilian Clinical Research Institute

Brief Summary

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

Detailed Description

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).

Study Timeline

• Status Verified: 2020-05
• Study First Submitted: 2020-05-08
• Study First Submitted QC: 2020-05-18
• Study First Posted: 2020-05-19
• Study Start: 2020-06-21
• Primary Completion: 2021-03-26
• Study Completion: 2021-05-30
• Last Update Submitted: 2021-06-08
• Last Update Posted: 2021-06-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 615

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Hierarchical composite endpoint composed of mortality, number of days alive, number of days in the hospital and number of days with oxygen therapy at the end of 30 days.	In 30 days	The primary objective will be analyzed using the win ratio approach comparing every participant of treatment group to every participant of control group to determine a winner.

Secondary Outcome Measures

Name	Time	Method
Incidence of stroke	In 30 days
Number of days using oxygen therapy	In 30 days
Peak of troponin	In 30 days
Peak of D-dimer	In 30 days
Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria	In 30 days	It will be considered the main safety endpoint
Incidence of acute myocardial infarction	In 30 days
Incidence of Venous thromboembolism	In 30 days

Trial Locations

Locations (36)

Centro de Pesquisa Clínica do Hospital de Clínicas da Universidade Federal de Uberlândia; 🇧🇷 Uberlândia, Minas Gerais, Brazil

Núcleo de Ciências de Saúde - Unidade de Pesquisa - Hospital Felício Rocho; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

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 Universitário da Universidade Estadual de Londrina; 🇧🇷 Londrina, Paraná, Brazil

Hospital Nereu Ramos; 🇧🇷 Florianópolis, Santa Catarina, Brazil

Praxis Pesquisa Médica; 🇧🇷 Santo André, São Paulo, 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

Hospital Agamenon Magalhães; 🇧🇷 Recife, Pernambuco, Brazil

Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - Unesp; 🇧🇷 Botucatu, São Paulo, Brazil

Hospital Regional do Litoral Norte; 🇧🇷 Caraguatatuba, São Paulo, Brazil

Hcor - Hospital do Coração; 🇧🇷 São Paulo, Brazil

Hospital Santa Paula; 🇧🇷 São Paulo, Brazil

Hospital Maternidade São Vicente de Paulo; 🇧🇷 Barbalha, Ceará, Brazil

Hospital Moinhos de Vento; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hospital de Amor de Barretos - (Pio XII); 🇧🇷 Barretos, São Paulo, Brazil

Hospital Regional de Registro; 🇧🇷 Registro, São Paulo, Brazil

Santa Casa de Misericórdia de Votuporanga; 🇧🇷 Votuporanga, São Paulo, Brazil

Centro Integrado de Pesquisa (CIP) - Hospital de Base de Rio Preto; 🇧🇷 São José Do Rio Preto, São Paulo, Brazil

BP - A Beneficência Portuguesa de São Paulo; 🇧🇷 São Paulo, Brazil

Hospital Samaritano Paulista; 🇧🇷 São Paulo, Brazil

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, Brazil

Hospital Moriah; 🇧🇷 São Paulo, Brazil

Instituto Dante Pazzanese de Cardiologia; 🇧🇷 São Paulo, Brazil

Hospital São Paulo; 🇧🇷 São Paulo, Brazil

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP-InCor-HCFMUSP; 🇧🇷 São Paulo, Brazil

Instituto de Assistência Médica ao Servidor Público Estadual de S. Paulo; 🇧🇷 São Paulo, Brazil

Hospital Naval Marcílio Dias; 🇧🇷 Rio de Janeiro, Brazil

Real Hospital Português de Beneficência em Pernambuco; 🇧🇷 Recife, Pernambuco, Brazil

Hospital Regional Hans Dieter Schmidt; 🇧🇷 Joinville, Santa Catarina, Brazil

Hospital Regional de São José dos Campos; 🇧🇷 São José Dos Campos, São Paulo, Brazil

Hospital Universitário São Francisco de Assis; 🇧🇷 Bragança Paulista, São Paulo, Brazil

Instituto Baia Sul de Ensino E Pesquisa Dr. Irineu May Brodbeck / Hospital Baía Sul; 🇧🇷 Florianópolis, Santa Catarina, Brazil