COVID-19
Conditions
Keywords
SARS-CoV-2, Heparin, Methylprednisolone, Anticoagulation, Coagulopathy, Respiratory failure
Brief summary
The COVID-19 pandemic has been spreading continuously, and in Brazil, until July 19, 2020, there have been more than 2,000,000 cases with more than 79,000 deaths, with daily increases. The present study proposes to evaluate the efficacy of methylprednisolone and heparin in treatment of patients with COVID-19 pneumonia in a randomized, controlled, 2x2 factorial study.
Interventions
DRUGMethylprednisolone
Methylprednisolone 0.5 mg/kg every 12 hours intravenously for the first 14 days; followed by 0.5 mg/kg/day from day 15 to day 21; followed by 0.25mg/kg/day from day 22 to day 25; followed by 0.125 mg/kg/day, from day 26 to day 28 of treatment.
DRUGHeparin
Enoxaparin 1 mg/kg subcutaneously every 12 hours (if creatinine clearance greater than 40ml/min) or Unfractionated heparin dosed to target activated partial thromboplastin time (aPTT) between 1.5 - 2.0 times the normal value (if creatinine clearance less or equal to 40ml/min). The treatment period with full-dose heparin will be 7 days. After 7 days of full-dose heparin, patients will continue using prophylactic dose of heparin, according to the standard treatment routine.
Sponsors
D'Or Institute for Research and Education
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of COVID-19 by RT-PCR or serology with presence of IgM positive antibodies; * Lung image (X-ray or chest CT) with involvement of at least 25% of the parenchyma; * O2 saturation in ambient air less than or equal to 93% * Alteration of inflammatory tests * D-Dimer above the reference value and * Elevation of C-reactive protein, ferritin or lactic dehydrogenase * Sign the consent form.
Exclusion criteria
* QT interval prolongation * Imminence of orotracheal intubation (intubation prediction in the first 4 hours after randomization) * Women who are pregnant or breastfeeding * Corticosteroid allergy or intolerance * Chronic corticosteroid users (prednisone equivalent \> 10 mg daily) * Patients diagnosed with cancer with increased bleeding potential * Patients in hemodialysis * History of peptic ulcer * Herpes zoster infection * History or active treatment of tuberculosis * Systemic fungal infection * Use of anticoagulation due to previous pathology * Glaucoma * Live virus vaccine up to 90 days before randomization * Known coagulopathy or thrombocytopenia (\<40,000/mm3) or hypofibrinogenemia (\< 50 mg/dL) * Recent bleeding * Another limiting comorbidity for administering the therapies provided for in this protocol in in researcher's opinion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of invasive mechanical ventilation | 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity assessment by ordinal severity scale | 3 days, 7 days, 14 days, 28 days after randomization | Severity assessment will be performed using the ordinal severity scale during hospitalization. |
| Severity assessment by SOFA score | 3 days, 7 days, 14 days, 28 days after randomization | Severity assessment will be performed using the SOFA score during hospitalization. |
| Length of hospital stay | 28 days | — |
| Length of stay in intensive care | 28 days | — |
| Death rate | 14 days, 28 days, 60 days, 90 days after randomization | — |
Countries
Brazil
Outcome results
None listed