Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)

Study Overview
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Brief Summary
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The main objective is to evaluate the efficacy and safety of three doses of tinzaparin (prophylactic, intermediate and therapeutic) in hospitalized patients with COVID-19 pneumonia.

Official Title
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Standard vs High Prophylactic Doses or Anticoagulation in Patients With High Risk of Thrombosis Admitted With COVID-19 Pneumonia (PROTHROMCOVID)

Conditions
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Covid19, Thrombosis

Intervention / Treatment
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* Drug: Tinzaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to hospital with COVID-19, PCR and/or Antigens Test + SARS-CoV-2 infection or (presence of infiltrate compatible with Chest X-ray or TC) Patients with, at least, one of the following evolution disease risk criteria: Sat 02<94% Need for oxygen therapy or pAO2/FiO2<300mmHg or estimated PaO2/FiO2 based on SpO2/FiO2<300 mmHg. DD>1000µg/L PCR >150mg/L IL6 >40pg/ml Age > 18 years Weight 50-100 Kg After receiving oral and written information about the study, patient must give Informed Consent duly signed and dated before performing any activity related to the study. Exclusion Criteria: Patients who need mechanical ventilation (invasive or non-invasive), high flow nasal cannula or admission to ICU at the moment of randomization. Current diagnosis of acute bronchial asthma attack. History or clinical suspicion of pulmonary fibrosis. Current diagnosis or suspicion of pulmonary thromboembolism or deep vein thrombosis. Patients who need anticoagulant treatment due to previous venous or arterial thrombotic disease, or due to atrial fibrillation. Patients with pneumonectomy or lobectomy. Renal failure with Glomerular filtration <30 ml/min/1.73m2 Patients with contraindication for anticoagulant treatment. Congenital bleeding disorders. Hypersensitivity to tinzaparin or UFH or some of its excipients. History of heparin-induced thrombocytopenia. Active bleeding or situation that predispose to bleeding. Moderate or severe anaemia (Hb<10 g/dl) Low platelet count < 80000/µl Patients with life expectancy less than 3 months due to primary disease evaluated by the physician. Patients currently intubated or intubated between the screening and the randomization. Pregnancy.

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: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tinzaparin 4500 UI/day<br>Procedure: Tinzaparin 4500 UI/day SC until hospital discharge. | Drug: Tinzaparin<br>* day subcutaneously • Follow-up phase 1 (Day 15 to day 30): The information is obtained at discharge and on day +14, + 28 on 30 days. The latter information is obtained from patients, from medical records or by telephone contact at the patient's home. • Follow-up phase 2 (At 3 months: Information is obtained from patients, medical records, or by telephone contact at the patient's home.<br>|
| Active Comparator: Tinzaparin 100 UI/Kg/day<br>Procedure: Tinzaparin 100 UI/Kg/day SC until hospital discharge. | Drug: Tinzaparin<br>* day subcutaneously • Follow-up phase 1 (Day 15 to day 30): The information is obtained at discharge and on day +14, + 28 on 30 days. The latter information is obtained from patients, from medical records or by telephone contact at the patient's home. • Follow-up phase 2 (At 3 months: Information is obtained from patients, medical records, or by telephone contact at the patient's home.<br>|
| Active Comparator: Tinzaparin 175 UI/Kg/day<br>Procedure: Tinzaparin 175 UI/Kg/day SC until hospital discharge. | Drug: Tinzaparin<br>* day subcutaneously • Follow-up phase 1 (Day 15 to day 30): The information is obtained at discharge and on day +14, + 28 on 30 days. The latter information is obtained from patients, from medical records or by telephone contact at the patient's home. • Follow-up phase 2 (At 3 months: Information is obtained from patients, medical records, or by telephone contact at the patient's home.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined variable that includes outcomes 2, 3 and 4 detailed below | Combined variable that includes outcomes 2, 3 and 4 detailed below (reduction of suspicion of systemic thrombotic symptomatic events and/or need for mechanical ventilation and/or death at day 30 after randomization). | 30 days | 
| Reduction of suspicion of systemic thrombotic symptomatic events | Reduction of symptomatic thrombotic events: rate of venous thromboembolism confirmed by objective test. | 30 days | 
| Use of Mechanical ventilation invasive or non invasive including high flow nasal cannula oxigen | Mechanical ventilation (invasive or non-invasive) free survival. | 30 days | 
| Overall survival at 30 days. | Overall survival at 30 days: number of deaths. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of bleedings and adverse reactions | Safety of the different strategies of prophylaxis and anticoagulation: number of bleedings and adverse reactions in each group: Evaluation of the following variables: Incidence of major bleeding, defined as meeting any of these criteria: a) fatal bleeding or bleeding that occurs in a critical area or organ (for example, intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome), b ) causes a drop in hemoglobin level of 20 g/L or more, or c) requires the transfusion of 2 or more units of whole blood or packed red blood cells. Incidence of clinically relevant non-major bleeding: manifest, spontaneous or post-traumatic bleeding, which does not meet the criteria for major bleeding but which in the judgment of the investigator is relevant. Incidence of clinically relevant bleeding: all major and non-major hemorrhages clinically relevant. Incidence of adverse reactions. | 90 days |