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

Sponsor

D'Or Institute for Research and Education (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04485429

Collaborator

(none)

Enrollment

Location

Arms

29.4

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Methylprednisolone Drug: Heparin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 20, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Methylprednisolone + Standard treatment Participants will receive the standard treatment and methylprednisolone.	Drug: Methylprednisolone 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.
Experimental: Full-dose heparin + Standard treatment Participants will receive the standard treatment and full-dose heparin,	Drug: Heparin 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.
Experimental: Methylprednisolone + Full-dose heparin + Standard treatment Participants will receive the standard treatment, methylprednisolone and full-dose heparin	Drug: Methylprednisolone 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. Drug: Heparin 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.
No Intervention: Standard treatment Participants will receive the standard treatment

Outcome Measures

Primary Outcome Measures

Rate of invasive mechanical ventilation [28 days]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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