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

NCT04485429 | Withdrawn Phase 3 DMC

• 1 other identifier: 31180820600005249
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Keywords

SARS-CoV-2; Heparin; Methylprednisolone; Anticoagulation; Coagulopathy; Respiratory failure

Outcome Measures

Primary Outcomes (1)

• Rate of invasive mechanical ventilation

  28 days

Secondary Outcomes (5)

• Severity assessment by ordinal severity scale

  3 days, 7 days, 14 days, 28 days after randomization

• Severity assessment by SOFA score

  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

Study Arms (4)

Methylprednisolone + Standard treatment

EXPERIMENTAL

Participants will receive the standard treatment and methylprednisolone.

Drug: Methylprednisolone

Full-dose heparin + Standard treatment

EXPERIMENTAL

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

Drug: Heparin

Methylprednisolone + Full-dose heparin + Standard treatment

EXPERIMENTAL

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

Drug: Methylprednisolone; Drug: Heparin

Standard treatment

NO INTERVENTION

Participants will receive the standard treatment

Interventions

Methylprednisolone 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.

Methylprednisolone + Full-dose heparin + Standard treatment; Methylprednisolone + Standard treatment

Heparin 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.

Full-dose heparin + Standard treatment; Methylprednisolone + Full-dose heparin + Standard treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• D'Or Institute for Research and Education: lead

Study Sites (1)

D'Or Institute for Research and Education

Rio de Janeiro, Brazil

Location

Related Publications (1)

• 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.

  PMID: 35244208 DERIVED

MeSH Terms

Conditions

COVID-19; Hemostatic Disorders; Respiratory Insufficiency

Interventions

Methylprednisolone; Heparin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Eduardo M Rego, MD, PhD

  D'Or Institute for Research and Education

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 24, 2020
• Study Start: July 20, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 11, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)