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

Coronavirus Infection Clinical Trial

— ACTION  

Official title:

Randomized Clinical Trial to Evaluate a Routine Full Anticoagulation Strategy in Patients With Coronavirus (COVID-19) - COALIZAO ACTION Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04394377
• Other study ID #: 002/2020
• Status: Completed
• Phase: Phase 4
• Start date: June 21, 2020
• Est. completion date: May 30, 2021

Study information

• Verified date: May 2020
• Source: Brazilian Clinical Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 615
• Est. completion date: May 30, 2021
• Est. primary completion date: March 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections

Intervention

Drug:
• Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed
Routine full anticoagulation strategy
• Group 2: control group with enoxaparin 40mg/d
Usual standard of care and currently have no indication of full anticoagulation.

Locations

Country	Name	City	State
Brazil	Hospital Maternidade São Vicente de Paulo	Barbalha	Ceará
Brazil	Hospital de Amor de Barretos - (Pio XII)	Barretos	São Paulo
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	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 Nereu Ramos	Florianópolis	Santa Catarina
Brazil	Instituto Baia Sul de Ensino E Pesquisa Dr. Irineu May Brodbeck / Hospital Baía Sul	Florianópolis	Santa Catarina
Brazil	Centro de Pesquisas Cardiológicas de Goiânia do Hospital das Clínicas (UFG)	Goiânia	Goiás
Brazil	Hospital Regional Hans Dieter Schmidt	Joinville	Santa Catarina
Brazil	Hospital Universitário da Universidade Estadual de Londrina	Londrina	Paraná
Brazil	Hospital Moinhos de Vento	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Agamenon Magalhães	Recife	Pernambuco
Brazil	Real Hospital Português de Beneficência em Pernambuco	Recife	Pernambuco
Brazil	Hospital Regional de Registro	Registro	São Paulo
Brazil	Hospital Naval Marcílio Dias	Rio de Janeiro
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	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	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	Centro de Ensino e Aperfeiçoamento em Pesquisa - CEAP	Serra	Espirito Santo
Brazil	Centro de Pesquisa Clínica do Hospital de Clínicas da Universidade Federal de Uberlândia	Uberlândia	Minas Gerais
Brazil	Santa Casa de Misericórdia de Votuporanga	Votuporanga	São Paulo

Sponsors (8)

Lead Sponsor	Collaborator
Brazilian Clinical Research Institute	Beneficência Portuguesa de São Paulo, Brazilian Research In Intensive Care Network, Hospital Alemão Oswaldo Cruz, Hospital do Coracao, Hospital Israelita Albert Einstein, Hospital Moinhos de Vento, Hospital Sirio-Libanes

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	In 30 days
Secondary	Incidence of Venous thromboembolism		In 30 days
Secondary	Incidence of acute myocardial infarction		In 30 days
Secondary	Incidence of stroke		In 30 days
Secondary	Number of days using oxygen therapy		In 30 days
Secondary	Peak of troponin		In 30 days
Secondary	Peak of D-dimer		In 30 days
Secondary	Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria	It will be considered the main safety endpoint	In 30 days