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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed
* Drug: Group 2: control group with enoxaparin 40mg/d


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>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<br>* Routine full anticoagulation strategy<br>|
| Other: Group 2<br>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<br>* Usual standard of care and currently have no indication of full anticoagulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Peak of D-dimer |  | In 30 days | 
| Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria | It will be considered the main safety endpoint | In 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV2, Anticoagulation, Coronavirus infection, COVID-19