Covid19
Conditions
Keywords
COVID-19, Heparin, Tocilizumab
Brief summary
The COVID-19 infection primarily manifests itself as a respiratory tract infection, although new evidence indicates that this disease has systemic involvement involving multiple systems including the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic and immune systems. Recent studies have shown that in its pathophysiology, inflammation and thrombogenesis predominate, especially in the severe forms of COVID-19. Thus, the investigators hypothesized that the use of heparin and tocilizumab could potencially reduce inflammation and thrombogenesis in patients with severe COVID-19 infection, improving patients outcomes and survival.
Interventions
DRUGTocilizumab
Tocilizumab infusion 8mg/kg/dose - Intravenous single dose.
Intravenous Non-Fractional Heparine (HNF) starting at 18UI/kg/h adjusted according to a nomogram to achieve an Activated Partial Thromboplastin Time (ATTP) from 1.5 To 2.0 times the reference Value; or Low Molecular Weight Heparin (LMWH) subcutaneous dosage of 1mg/kg per dose every 12 hours
DRUGHeparin - Prophylactic dosage
Subcutaneous Non-Fractional Heparine 5000U every 8 hours OR Subcutaneous Low Molecular Weight (LMWH) 40mg/day.
Sponsors
Conselho Nacional de Desenvolvimento Científico e Tecnológico
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years; * Informed consent form signed by the patient or guardian or by audio with the guardian; * Positive result for COVID-19 in PCR (polymerase chain reaction) in nasopharyngeal swab or tracheal secretion up to 10 days before the inclusion and radiological evidence of COVID-19, by chest radiography or chest computed tomography; * Need for ≥ 4 L of supplemental oxygen to maintain peripheral oxygen saturation equal to or greater than 93% or need for invasive mechanical ventilation.
Exclusion criteria
* Risk of bleeding: * Clinical: active bleeding, major surgery in the last 30 days, gastrointestinal bleeding within 30 days; * Laboratory: platelet count \<50,000, INR\> 2 or APTT\> 50s; * Known or suspected adverse reaction to UFH, including heparin-induced thrombocytopenia (TIH); * Adverse reaction or allergy to tocilizumab; * Use of any of the following treatments: UFH to treat a thrombotic event within 12 hours before inclusion; HPBM in therapeutic dose within 12 hours before inclusion; warfarin (if used 7 days before and if INR greater than 2; thrombolytic therapy within 3 days before; and use of glycoprotein IIb / IIIa inhibitors within the previous 7 days; * Pregnant or lactating; * Absolute indication of anticoagulation due to atrial fibrillation or diagnosed thromboembolic event; * Refusal by family members and / or patient; * Active tuberculosis; * Bacterial infection confirmed by culture; * Neutropenia (\<1000 neutrophils / mm3); * Use of another immunosuppressive therapy that is not a corticosteroid; * Septic shock.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with clinical improvement | 30 days | Proportion of patients with clinical improvement in 30 days, defined by hospital discharge or a reduction of at least 2 points compared to baseline on the ordinal scale recommended by the World Health Organization: 1. Not hospitalized, with no limitations on activities; 2. Not hospitalized, but limited to activities; 3. Hospitalized, with no need for supplemental oxygen; 4. Hospitalized, needing supplemental oxygen; 5. Hospitalized, requiring high flow oxygen therapy, non-invasive mechanical ventilation or both; 6. Hospitalized, requiring ECMO, invasive mechanical ventilation or both; 7. Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of invasive mechanical ventilation | 30 days | Time requiring invasive mechanical ventilation |
| Duration of vasopressor use | 30 days | Time of use of vasopressors |
| Renal failure by AKIN criteria | 30 days | Renal failure by AKIN criteria in 30 days |
| Hospital and ICU length of stay; | 30 days | Number of days in hospital and ICU |
| Incidence of venous thromboembolism | 30 days | Deep vein thrombosis and pulmonary embolism |
| Mortality | 30, 60 and 90 days | Mortality rate |
| Incidence of cardiovascular complications | 30 days | Myocardial injury; Acute myocardial infarction; Cardiogenic shock; arrhythmias; Myocarditis; Pericarditis; Ventricular dysfunction. |
Countries
Brazil
Outcome results
None listed