Clinical trial NCT04394377: Full Anticoagulation Versus Prophylaxis in COVID-19: COALIZAO ACTION Trial
Official title: Randomized Clinical Trial to Evaluate a Routine Full Anticoagulation Strategy in Patients With Coronavirus (COVID-19) - COALIZAO ACTION Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronavirus Infection
Keywords: SARS-CoV2
Anticoagulation
Coronavirus infection
COVID-19
Lead sponsor: Brazilian Clinical Research Institute
Sponsor class: OTHER
Collaborators: name: Hospital Israelita Albert Einstein
name: Hospital do Coracao
name: Hospital Sirio-Libanes
name: Hospital Moinhos de Vento
name: Hospital Alemão Oswaldo Cruz
name: Beneficência Portuguesa de São Paulo
name: Brazilian Research In Intensive Care Network
First posted: 2020-05-19
Enrollment: 615
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: 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.
timeFrame: In 30 days
Secondary outcomes:
measure: Incidence of Venous thromboembolism
timeFrame: In 30 days
measure: Incidence of acute myocardial infarction
timeFrame: In 30 days
measure: Incidence of stroke
timeFrame: In 30 days
measure: Number of days using oxygen therapy
timeFrame: In 30 days
measure: Peak of troponin
timeFrame: In 30 days
measure: Peak of D-dimer
timeFrame: In 30 days
measure: Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria
timeFrame: In 30 days
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Centro de Estudos Clínicos do Hospital Cárdio Pulmonar
state: Bahia
city: Salvador
country: Brazil
facility: Instituto de Ensino e Pesquisa do Hospital da Bahia
state: Bahia
city: Salvador
country: Brazil
facility: Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel
state: Bahia
city: Barbalha
country: Brazil
facility: Hospital Maternidade São Vicente de Paulo
state: Ceará
city: Serra
country: Brazil
facility: Centro de Ensino e Aperfeiçoamento em Pesquisa - CEAP
state: Espirito Santo
city: Goiânia
country: Brazil
facility: Centro de Pesquisas Cardiológicas de Goiânia do Hospital das Clínicas (UFG)
state: Goiás
city: Belo Horizonte
country: Brazil
facility: Hospital Vera Cruz
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Núcleo de Ciências de Saúde - Unidade de Pesquisa - Hospital Felício Rocho
state: Minas Gerais
city: Uberlândia
country: Brazil
facility: Centro de Pesquisa Clínica do Hospital de Clínicas da Universidade Federal de Uberlândia
state: Minas Gerais
city: Londrina
country: Brazil
facility: Hospital Universitário da Universidade Estadual de Londrina
state: Paraná
city: Recife
country: Brazil
facility: Hospital Agamenon Magalhães
state: Pernambuco
city: Recife
country: Brazil
facility: Real Hospital Português de Beneficência em Pernambuco
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: Rio Grande Do Sul
city: Florianópolis
country: Brazil
facility: Hospital Nereu Ramos
state: Santa Catarina
city: Florianópolis
country: Brazil
facility: Instituto Baia Sul de Ensino E Pesquisa Dr. Irineu May Brodbeck / Hospital Baía Sul
state: Santa Catarina
city: Joinville
country: Brazil
facility: Hospital Regional Hans Dieter Schmidt
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital de Amor de Barretos - (Pio XII)
state: São Paulo
city: Botucatu
country: Brazil
facility: Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - Unesp
state: São Paulo
city: Bragança Paulista
country: Brazil
facility: Hospital Universitário São Francisco de Assis
state: São Paulo
city: Caraguatatuba
country: Brazil
facility: Hospital Regional do Litoral Norte
state: São Paulo
city: Registro
country: Brazil
facility: Hospital Regional de Registro
state: São Paulo
city: Santo André
country: Brazil
facility: Praxis Pesquisa Médica
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Centro Integrado de Pesquisa (CIP) - Hospital de Base de Rio Preto
state: São Paulo
city: São José Dos Campos
country: Brazil
facility: Hospital Regional de São José dos Campos
state: São Paulo
city: Votuporanga
country: Brazil
facility: Santa Casa de Misericórdia de Votuporanga
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Hospital Naval Marcílio Dias
city: São Paulo
country: Brazil
facility: BP - A Beneficência Portuguesa de São Paulo
city: São Paulo
country: Brazil
facility: Hcor - Hospital do Coração
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: São Paulo
country: Brazil
facility: Hospital Moriah
city: São Paulo
country: Brazil
facility: Hospital Samaritano Paulista
city: São Paulo
country: Brazil
facility: Hospital Santa Paula
city: São Paulo
country: Brazil
facility: Hospital São Paulo
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
city: São Paulo
country: Brazil
facility: Instituto de Assistência Médica ao Servidor Público Estadual de S. Paulo
city: São Paulo
country: Brazil
facility: Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP-InCor-HCFMUSP
Study officials:
affiliation: BCRI
name: Renato D. Lopes, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.