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Coronavirus InfectionPhase 4ACTIONNCT04394377

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

A Phase 4 study testing Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed in people with Coronavirus Infection, run by Brazilian Clinical Research Institute at 36 sites in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronavirus Infection
What is being tested?
Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
615 participants
Where
36 sitesBrazil
Study dates
21 Jun 2020to 30 May 2021
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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;
Show all 16Show fewer
  • 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.

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

Brazil36 sites

  • Hospital Maternidade São Vicente de Paulo

    Barbalha, Ceará

  • Hospital de Amor de Barretos - (Pio XII)

    Barretos, São Paulo

  • Hospital Vera Cruz

    Belo Horizonte, Minas Gerais

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

    Belo Horizonte, Minas Gerais

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

    Botucatu, São Paulo

  • Hospital Universitário São Francisco de Assis

    Bragança Paulista, São Paulo

  • Hospital Regional do Litoral Norte

    Caraguatatuba, São Paulo

  • Hospital Nereu Ramos

    Florianópolis, Santa Catarina

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

    Florianópolis, Santa Catarina

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

    Goiânia, Goiás

  • Hospital Regional Hans Dieter Schmidt

    Joinville, Santa Catarina

  • Hospital Universitário da Universidade Estadual de Londrina

    Londrina, Paraná

  • Hospital Moinhos de Vento

    Porto Alegre, Rio Grande do Sul

  • Hospital Agamenon Magalhães

    Recife, Pernambuco

  • Real Hospital Português de Beneficência em Pernambuco

    Recife, Pernambuco

  • Hospital Regional de Registro

    Registro, São Paulo

  • Hospital Naval Marcílio Dias

    Rio de Janeiro

  • Centro de Estudos Clínicos do Hospital Cárdio Pulmonar

    Salvador, Estado de Bahia

  • Instituto de Ensino e Pesquisa do Hospital da Bahia

    Salvador, Estado de Bahia

  • Santa Casa de Misericórdia da Bahia - Hospital Santa Izabel

    Salvador, Estado de Bahia

  • Praxis Pesquisa Médica

    Santo André, São Paulo

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

    São José do Rio Preto, São Paulo

  • Hospital Regional de São José dos Campos

    São José dos Campos, São Paulo

  • BP - A Beneficência Portuguesa de São Paulo

    São Paulo

  • Hcor - Hospital do Coração

    São Paulo

  • Hospital Israelita Albert Einstein

    São Paulo

  • Hospital Moriah

    São Paulo

  • Hospital Samaritano Paulista

    São Paulo

  • Hospital Santa Paula

    São Paulo

  • Hospital São Paulo

    São Paulo

  • Instituto Dante Pazzanese de Cardiologia

    São Paulo

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

    São Paulo

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

    São Paulo

  • Centro de Ensino e Aperfeiçoamento em Pesquisa - CEAP

    Serra, Espírito Santo

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

    Uberlândia, Minas Gerais

  • Santa Casa de Misericórdia de Votuporanga

    Votuporanga, São Paulo

Other trials in Brazil

About this study

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

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

Read the 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).

Being tested
Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed, Group 2: control group with enoxaparin 40mg/d
Keywords
SARS-CoV2, Anticoagulation, Coronavirus infection, COVID-19
Medical subject headings
Coronavirus Infections, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Routine full anticoagulation strategy

  • Group 2: control group with enoxaparin 40mg/dDrug

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

Study groups in NCT04394377
Study groupRoleWhat they receive
Group 1OtherThe 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).
Receives: Drug: Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed
Group 2OtherPatients 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.
Receives: Drug: Group 2: control group with enoxaparin 40mg/d

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: In 30 days

Secondary outcomes (7)

  1. Incidence of Venous thromboembolism

    Measured: In 30 days

  2. Incidence of acute myocardial infarction

    Measured: In 30 days

  3. Incidence of stroke

    Measured: In 30 days

  4. Number of days using oxygen therapy

    Measured: In 30 days

  5. Peak of troponin

    Measured: In 30 days

  6. Peak of D-dimer

    Measured: In 30 days

  7. Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria

    It will be considered the main safety endpoint

    Measured: In 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2020
  2. Study start21 Jun 2020
  3. Primary completion26 Mar 2021
  4. Study completion30 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
615 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04394377
Sponsor's protocol ID
002/2020
Acronym
ACTION
Status last verified
May 2020
First submitted
8 May 2020
Last updated
10 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All data provided during study is anonymized to respect the privacy of patients who have participated in the trial in line with applicable regulations.

Publications

  • 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.

    PubMed 38762708

  • 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: a rapid review. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

    PubMed 35244208

  • 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.

    PubMed 34097856

  • 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.

    PubMed 33891907

  • 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.

    PubMed 33502773

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed in people with Coronavirus Infection, run by Brazilian Clinical Research Institute at 36 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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. (time frame: In 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04394377, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.

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