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

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ClinicalTrials.gov Identifier: NCT04394377
Recruitment Status : Not yet recruiting
First Posted : May 19, 2020
Last Update Posted : May 22, 2020
Sponsor:
Collaborators:
Hospital Israelita Albert Einstein
Hospital do Coracao
Hospital Sirio-Libanes
Hospital Moinhos de Vento
Hospital Alemão Oswaldo Cruz
Beneficência Portuguesa de São Paulo
Brazilian Research In Intensive Care Network
Information provided by (Responsible Party):
Brazilian Clinical Research Institute

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


Condition or disease Intervention/treatment Phase
Coronavirus Infection Drug: Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed Drug: Group 2: control group with enoxaparin 40mg/d Phase 4

Detailed Description:
Patients who meet the eligibility criteria (patients admitted to hospital with confirmed COVID-19 infection associated to D-dimer > 3 times the ULN) will be invited to participate in the proposed study and, following the application of the informed consent form, 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); and group 2 will follow the usual standard care without full anticoagulation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial to Evaluate a Routine Full Anticoagulation Strategy in Patients With Coronavirus (COVID-19) - COALIZAO ACTION Trial
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).
Drug: Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed
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.
Drug: Group 2: control group with enoxaparin 40mg/d
Usual standard of care and currently have no indication of full anticoagulation.




Primary Outcome Measures :
  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. [ Time Frame: 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 Outcome Measures :
  1. Incidence of Venous thromboembolism [ Time Frame: In 30 days ]
  2. Incidence of acute myocardial infarction [ Time Frame: In 30 days ]
  3. Incidence of stroke [ Time Frame: In 30 days ]
  4. Number of days using oxygen therapy [ Time Frame: In 30 days ]
  5. Peak of troponin [ Time Frame: In 30 days ]
  6. Peak of D-dimer [ Time Frame: In 30 days ]
  7. Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria [ Time Frame: In 30 days ]
    It will be considered the main safety endpoint



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with confirmed diagnosis of COVID-19 admitted to hospital;
  • Onset of symptoms leading to hospitalization <14 days;
  • Patients ≥ 18 year old;
  • D-dimer ≥ 3 x the upper limit of normal;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394377


Contacts
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Contact: Renato D. Lopes, MD, PhD 55 11 5904 7339 renato.lopes@duke.edu

Sponsors and Collaborators
Brazilian Clinical Research Institute
Hospital Israelita Albert Einstein
Hospital do Coracao
Hospital Sirio-Libanes
Hospital Moinhos de Vento
Hospital Alemão Oswaldo Cruz
Beneficência Portuguesa de São Paulo
Brazilian Research In Intensive Care Network
Investigators
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Study Chair: Renato D. Lopes, MD, PhD BCRI
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Responsible Party: Brazilian Clinical Research Institute
ClinicalTrials.gov Identifier: NCT04394377    
Other Study ID Numbers: 002/2020
First Posted: May 19, 2020    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All data provided during study is anonymized to respect the privacy of patients who have participated in the trial in line with applicable regulations.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Brazilian Clinical Research Institute:
SARS-CoV2
Anticoagulation
Coronavirus infection
COVID-19
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Heparin
Enoxaparin
Calcium heparin
Rivaroxaban
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors