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

Conditions

Coronavirus Infection

Keywords

SARS-CoV2, Anticoagulation, Coronavirus infection, COVID-19

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).

de Barros E Silva PGM, Furtado RHM, de Alcântara 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, Conceição-Souza GE, Armaganijan L, Guimarães PO, Rosa RG, Azevedo LCP, Alexander JH, Avezum A, Berwanger O, Cavalcanti AB, Lopes RD, ACTION Coalition COVID-19 Brazil IV Investigators.

2024-05-181 citations

10.1007/s11239-024-02995-y

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

Gilson Soares Feitosa-Filho, Gabriella S. Sodré, Juliane Penalva C. Serra, Rhanniel Theodorus-Villar, Tatiana Otero Mendelez et al. (8 authors)

Revista Científica Hospital Santa Izabel2021-08-093 citations

10.35753/rchsi.v5i2.211

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.

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 Alcântara 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, Conceição-Souza GE, Armaganijan L, Guimarães PO, Rosa RG, Azevedo LCP, Alexander JH, Avezum A, Cavalcanti AB, Berwanger O, ACTION Coalition COVID-19 Brazil IV Investigators.

2021-06-04364 citations

10.1016/s0140-6736(21)01203-4

Interventions

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

Routine full anticoagulation strategy

DRUGGroup 2: control group with enoxaparin 40mg/d

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Incidence of acute myocardial infarction	In 30 days	—
Incidence of stroke	In 30 days	—
Number of days using oxygen therapy	In 30 days	—
Incidence of Venous thromboembolism	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
Peak of troponin	In 30 days	—

Countries

Brazil

Outcome results

None listed