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

NCT ID: NCT04394377

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 615 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-21
• Study Completion Date: 2021-05-30

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).

Conditions

Coronavirus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group 1

The routine full anticoagulation strategy will be applied for 30 days. In this strategy, full anticoagulation therapy will be maintained for all patients randomized to group 1 and, depending on the patient's clinical condition, there will be 2 possible routes of administration (oral or parenteral):

• Oral: Rivaroxaban 20 mg 1 x daily (adjust the dose to 15 mg 1x daily if ClCr between 30 and 49ml/min and/or concomitant use of azithromycin);
• Parenteral: Enoxaparin 1 mg/kg every 12 hours subcutaneously or Unfractionated heparin (preferable option for patients progressing with disseminated intravascular coagulation).

Group Type: OTHER

Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed

Intervention Type: DRUG

Routine full anticoagulation strategy

Group 2

Patients in this group will receive the usual standard management and currently have no indication of full anticoagulation. Venous thromboembolism (VTE) prophylaxis should be used in group 2 (usual standard of care) as recommended by guidelines.

Group Type: OTHER

Group 2: control group with enoxaparin 40mg/d

Intervention Type: DRUG

Usual standard of care and currently have no indication of full anticoagulation.

Interventions

Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed

Routine full anticoagulation strategy

Intervention Type: DRUG

Group 2: control group with enoxaparin 40mg/d

Usual standard of care and currently have no indication of full anticoagulation.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: collaborator

Hospital do Coracao

OTHER

Sponsor Role: collaborator

Hospital Sirio-Libanes

OTHER

Sponsor Role: collaborator

Hospital Moinhos de Vento

OTHER

Sponsor Role: collaborator

Hospital Alemão Oswaldo Cruz

OTHER

Sponsor Role: collaborator

Beneficência Portuguesa de São Paulo

OTHER

Sponsor Role: collaborator

Brazilian Research In Intensive Care Network

NETWORK

Sponsor Role: collaborator

Brazilian Clinical Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renato D. Lopes, MD, PhD

Role: STUDY_CHAIR

BCRI

Locations

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Centro de Ensino e Aperfeiçoamento em Pesquisa - CEAP

Serra, Espírito Santo, Brazil

Centro de Estudos Clínicos do Hospital Cárdio Pulmonar

Salvador, Estado de Bahia, Brazil

Instituto de Ensino e Pesquisa do Hospital da Bahia

Salvador, Estado de Bahia, Brazil

Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel

Salvador, Estado de Bahia, 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

Countries

Brazil

References

de Barros E Silva PGM, Furtado RHM, de Alcantara Chaud MS, Macedo AVS, Bronhara B, Damiani LP, Barbosa LM, Suiama MA, Ramacciotti E, de Aquino Martins P, de Oliveira AL, Nunes VS, Ritt LEF, Rocha AT, Tramujas L, Santos SV, Diaz DRA, Viana LS, Melro LMG, Figueiredo EL, Neuenschwander FC, Dracoulakis MDA, Lima RGSD, de Souza Dantas VC, Fernandes ACS, Gebara OCE, Hernandes ME, Queiroz DAR, Veiga VC, Canesin MF, de Faria LM, Feitosa-Filho GS, Gazzana MB, Liporace IL, de Oliveira Twardowsky A, Maia LN, Machado FR, de Matos Soeiro A, Conceicao-Souza GE, Armaganijan L, Guimaraes PO, Rosa RG, Azevedo LCP, Alexander JH, Avezum A, Berwanger O, Cavalcanti AB, Lopes RD; ACTION Coalition COVID-19 Brazil IV Investigators. Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial. J Thromb Thrombolysis. 2024 Aug;57(6):1031-1039. doi: 10.1007/s11239-024-02995-y. Epub 2024 May 18.

Reference Type: DERIVED

PMID: 38762708 (View on PubMed)

Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Reference Type: DERIVED

PMID: 35244208 (View on PubMed)

Lopes RD, de Barros E Silva PGM, Furtado RHM, Macedo AVS, Bronhara B, Damiani LP, Barbosa LM, de Aveiro Morata J, Ramacciotti E, de Aquino Martins P, de Oliveira AL, Nunes VS, Ritt LEF, Rocha AT, Tramujas L, Santos SV, Diaz DRA, Viana LS, Melro LMG, de Alcantara Chaud MS, Figueiredo EL, Neuenschwander FC, Dracoulakis MDA, Lima RGSD, de Souza Dantas VC, Fernandes ACS, Gebara OCE, Hernandes ME, Queiroz DAR, Veiga VC, Canesin MF, de Faria LM, Feitosa-Filho GS, Gazzana MB, Liporace IL, de Oliveira Twardowsky A, Maia LN, Machado FR, de Matos Soeiro A, Conceicao-Souza GE, Armaganijan L, Guimaraes PO, Rosa RG, Azevedo LCP, Alexander JH, Avezum A, Cavalcanti AB, Berwanger O; ACTION Coalition COVID-19 Brazil IV Investigators. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021 Jun 12;397(10291):2253-2263. doi: 10.1016/S0140-6736(21)01203-4. Epub 2021 Jun 4.

Reference Type: DERIVED

PMID: 34097856 (View on PubMed)

Lopes RD, de Barros E Silva PGM, Furtado RHM, Macedo AVS, Ramacciotti E, Damini LP, Bronhara B, Cavalcanti AB, Rosa RG, Azevedo LCP, Veiga VC, Machado FR, Ritt LE, Martins PA, Alexander JH, Avezum A, Berwanger O; Coalition COVID-19 Brazil IV Investigators. Randomized clinical trial to evaluate a routine full anticoagulation Strategy in Patients with Coronavirus Infection (SARS-CoV2) admitted to hospital: Rationale and design of the ACTION (AntiCoagulaTlon cOroNavirus)-Coalition IV trial. Am Heart J. 2021 Aug;238:1-11. doi: 10.1016/j.ahj.2021.04.005. Epub 2021 Apr 20.

Reference Type: DERIVED

PMID: 33891907 (View on PubMed)

Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

Reference Type: DERIVED

PMID: 33502773 (View on PubMed)

Other Identifiers

002/2020

Identifier Type: -

Identifier Source: org_study_id