Efficacy Assessment of Methylprednisolone and Heparin in Patients With COVID-19 Pneumonia

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy Assessment of Methylprednisolone and Heparin in Patients With COVID-19 Pneumonia: A Randomized, Controlled, 2x2 Factorial Study

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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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

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylprednisolone + Standard treatment<br>Participants will receive the standard treatment and methylprednisolone. | Drug: Methylprednisolone<br>* 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.<br>|
| Experimental: Full-dose heparin + Standard treatment<br>Participants will receive the standard treatment and full-dose heparin, | Drug: Heparin<br>* 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.<br>|
| Experimental: Methylprednisolone + Full-dose heparin + Standard treatment<br>Participants will receive the standard treatment, methylprednisolone and full-dose heparin | Drug: Methylprednisolone<br>* 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.<br>Drug: Heparin<br>* 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.<br>|
| No Intervention: Standard treatment<br>Participants will receive the standard treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of invasive mechanical ventilation |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity assessment by ordinal severity scale | Severity assessment will be performed using the ordinal severity scale during hospitalization. | 3 days, 7 days, 14 days, 28 days after randomization | 
| Severity assessment by SOFA score | Severity assessment will be performed using the SOFA score during hospitalization. | 3 days, 7 days, 14 days, 28 days after randomization | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Heparin, Methylprednisolone, Anticoagulation, Coagulopathy, Respiratory failure