NCT04394377

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
615

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jun 2020

Shorter than P25 for phase_4

Geographic Reach
1 country

36 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 8, 2020

Completed
11 days until next milestone

First Posted

Study publicly available on registry

May 19, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

June 21, 2020

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 26, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2021

Completed
Last Updated

June 10, 2021

Status Verified

May 1, 2020

Enrollment Period

9 months

First QC Date

May 8, 2020

Last Update Submit

June 8, 2021

Conditions

Keywords

SARS-CoV2AnticoagulationCoronavirus infectionCOVID-19

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (7)

  • Incidence of Venous thromboembolism

    In 30 days

  • Incidence of acute myocardial infarction

    In 30 days

  • Incidence of stroke

    In 30 days

  • Number of days using oxygen therapy

    In 30 days

  • Peak of troponin

    In 30 days

  • +2 more secondary outcomes

Study Arms (2)

Group 1

OTHER

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).

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

Group 2

OTHER

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.

Drug: Group 2: control group with enoxaparin 40mg/d

Interventions

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

Group 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (36)

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Location

Centro de Ensino e Aperfeiçoamento em Pesquisa - CEAP

Serra, Espírito Santo, Brazil

Location

Centro de Estudos Clínicos do Hospital Cárdio Pulmonar

Salvador, Estado de Bahia, Brazil

Location

Instituto de Ensino e Pesquisa do Hospital da Bahia

Salvador, Estado de Bahia, Brazil

Location

Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel

Salvador, Estado de Bahia, Brazil

Location

Centro de Pesquisas Cardiológicas de Goiânia do Hospital das Clínicas (UFG)

Goiânia, Goiás, Brazil

Location

Hospital Vera Cruz

Belo Horizonte, Minas Gerais, Brazil

Location

Núcleo de Ciências de Saúde - Unidade de Pesquisa - Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

Location

Centro de Pesquisa Clínica do Hospital de Clínicas da Universidade Federal de Uberlândia

Uberlândia, Minas Gerais, Brazil

Location

Hospital Universitário da Universidade Estadual de Londrina

Londrina, Paraná, Brazil

Location

Hospital Agamenon Magalhães

Recife, Pernambuco, Brazil

Location

Real Hospital Português de Beneficência em Pernambuco

Recife, Pernambuco, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital Nereu Ramos

Florianópolis, Santa Catarina, Brazil

Location

Instituto Baia Sul de Ensino E Pesquisa Dr. Irineu May Brodbeck / Hospital Baía Sul

Florianópolis, Santa Catarina, Brazil

Location

Hospital Regional Hans Dieter Schmidt

Joinville, Santa Catarina, Brazil

Location

Hospital de Amor de Barretos - (Pio XII)

Barretos, São Paulo, Brazil

Location

Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - Unesp

Botucatu, São Paulo, Brazil

Location

Hospital Universitário São Francisco de Assis

Bragança Paulista, São Paulo, Brazil

Location

Hospital Regional do Litoral Norte

Caraguatatuba, São Paulo, Brazil

Location

Hospital Regional de Registro

Registro, São Paulo, Brazil

Location

Praxis Pesquisa Médica

Santo André, São Paulo, Brazil

Location

Centro Integrado de Pesquisa (CIP) - Hospital de Base de Rio Preto

São José do Rio Preto, São Paulo, Brazil

Location

Hospital Regional de São José dos Campos

São José dos Campos, São Paulo, Brazil

Location

Santa Casa de Misericórdia de Votuporanga

Votuporanga, São Paulo, Brazil

Location

Hospital Naval Marcílio Dias

Rio de Janeiro, Brazil

Location

BP - A Beneficência Portuguesa de São Paulo

São Paulo, Brazil

Location

Hcor - Hospital do Coração

São Paulo, Brazil

Location

Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

Hospital Moriah

São Paulo, Brazil

Location

Hospital Samaritano Paulista

São Paulo, Brazil

Location

Hospital Santa Paula

São Paulo, Brazil

Location

Hospital São Paulo

São Paulo, Brazil

Location

Instituto Dante Pazzanese de Cardiologia

São Paulo, Brazil

Location

Instituto de Assistência Médica ao Servidor Público Estadual de S. Paulo

São Paulo, Brazil

Location

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP-InCor-HCFMUSP

São Paulo, Brazil

Location

Related Publications (5)

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Coronavirus InfectionsCOVID-19

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Coronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesInfectionsPneumonia, ViralPneumoniaRespiratory Tract InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-WeightHeparinGlycosaminoglycansPolysaccharidesCarbohydrates

Study Officials

  • Renato D. Lopes, MD, PhD

    BCRI

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 8, 2020

First Posted

May 19, 2020

Study Start

June 21, 2020

Primary Completion

March 26, 2021

Study Completion

May 30, 2021

Last Updated

June 10, 2021

Record last verified: 2020-05

Data Sharing

IPD Sharing
Will share

All data provided during study is anonymized to respect the privacy of patients who have participated in the trial in line with applicable regulations.

Locations