Methylprednisolone in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome in Covid-19 (MetCOVID)

Efficacy of Injectable Methylprednisolone Sodium Succinate in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome Under the New Coronavirus (SARS-CoV2): a Phase IIb, Randomized, Double-blind, Placebo-controlled, Clinical Trial.

This is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 416 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MP (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

Study Overview

• Status: Completed
• Conditions: SARS-CoV Infection; Severe Acute Respiratory Syndrome (SARS) Pneumonia
• Intervention / Treatment: Drug: Methylprednisolone Sodium Succinate; Drug: Placebo solution

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Amazonas
    • Manaus, Amazonas, Brazil, 69093-415
      • Hospital e Pronto Socorro Delphina Rinaldi Abdel Aziz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Suspected cases of COVID-19, from clinical and radiological data, during the pandemic;
2. Adult aged 18 years or older, at the time of inclusion (children under 18 will not be included due to the recognized lower lethality in previous published studies, and the difficulty of consent in the context of an emergency in public health);
3. SpO2 ≤ 94% in room air OR in use supplementary oxygen OR under invasive mechanical ventilation

Exclusion Criteria:

1. History of hypersensitivity to MPS;
2. People living with HIV and AIDS;
3. Chronic use of corticosteroids or immunosuppressive agents;
4. Pregnancy or breastfeeding;
5. Decompensated cirrhosis;
6. Chronic renal failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methylprednisolone; 0.5mg/kg injectable methylprednisolone sodium succinate, twice daily, for 5 days.	Drug: Methylprednisolone Sodium Succinate; injectable solution at a dose of 0.5mg/kg; Other Names: methylprednisolone
Placebo Comparator: Placebo; Saline solution, twice daily, for 5 days. Injectable.	Drug: Placebo solution; injectable saline solution; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate at day 28	Mortality rate on day 28, after randomization	on day 28, after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate on days 7, 14 and 28	Proportion of patient that died on days 7, 14 and 28.	after randomization, up to 28 days.
Incidence of orotracheal intubation	proportion of patients requiring orotracheal intubation	after randomization, up to 7 days.
Change in oxygenation index	Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.	after randomization, up to 7 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spirometry (exploratory outcome)	Forced expiratory capacity at the first second of exhalation (FEV1) in liters	120 days after randomization
Spirometry (exploratory outcome)	Forced vital capacity (FVC) in liters	120 days after randomization
Spirometry (exploratory outcome)	FEV1/FVC ratio	120 days after randomization
Spirometry (exploratory outcome)	Forced expiratory flow (FEF) in cmH2O	120 days after randomization
Spirometry (exploratory outcome)	Peak expiratory flow (PEF) in cmH2O	120 days after randomization

Collaborators and Investigators

• Sponsor: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Publications and helpful links

General Publications

• Barros CMSS, Freire RS, Frota E, Rezende Santos AG, Farias MEL, Rodrigues MGA, Silva BM, Prado Jeronimo CM, Netto RLA, Silva Borba MG, Baia-da-Silva D, Brito-Sousa JD, Xavier MS, Araujo-Alexandre MA, Sampaio VS, Melo GC, Areas GT, Hajjar LA, Monteiro WM, Gomes Naveca F, Costa FTM, Val FFA, Lacerda MVG; Metcovid team. Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial. Front Med (Lausanne). 2021 Nov 30;8:758405. doi: 10.3389/fmed.2021.758405. eCollection 2021.
• Jeronimo CMP, Farias MEL, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Safe IP, Borba MGS, Netto RLA, Maciel ABS, Neto JRS, Oliveira LB, Figueiredo EFG, Oliveira Dinelly KM, de Almeida Rodrigues MG, Brito M, Mourao MPG, Pivoto Joao GA, Hajjar LA, Bassat Q, Romero GAS, Naveca FG, Vasconcelos HL, de Araujo Tavares M, Brito-Sousa JD, Costa FTM, Nogueira ML, Baia-da-Silva DC, Xavier MS, Monteiro WM, Lacerda MVG; Metcovid Team. Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e373-e381. doi: 10.1093/cid/ciaa1177.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2020
• Primary Completion (Actual): June 16, 2020
• Study Completion (Actual): October 20, 2020

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Covid-19; Coronavirus; Corticosteroid; methylprednisolone; Severe Acute Respiratory Syndrome (SARS) Pneumonia
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease; Severe Acute Respiratory Syndrome; Syndrome; Pneumonia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: CAEE: 30615920.2.0000.0005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all patient data will be shared after study publication
• IPD Sharing Time Frame: after study publication.
• IPD Sharing Access Criteria: upon formal request.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No