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

NCT ID: NCT04485429

Last Updated: 2021-08-11

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-20
• Study Completion Date: 2022-12-31

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Methylprednisolone + Standard treatment

Participants will receive the standard treatment and methylprednisolone.

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

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.

Full-dose heparin + Standard treatment

Participants will receive the standard treatment and full-dose heparin,

Group Type: EXPERIMENTAL

Heparin

Intervention Type: DRUG

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.

Methylprednisolone + Full-dose heparin + Standard treatment

Participants will receive the standard treatment, methylprednisolone and full-dose heparin

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

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.

Heparin

Intervention Type: DRUG

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.

Standard treatment

Participants will receive the standard treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

D'Or Institute for Research and Education

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eduardo M Rego, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

D'Or Institute for Research and Education

Locations

D'Or Institute for Research and Education

Rio de Janeiro, , Brazil

Countries

Brazil

References

Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Reference Type: DERIVED

PMID: 35244208 (View on PubMed)

Other Identifiers

31180820600005249

Identifier Type: -

Identifier Source: org_study_id