Glucocorticoid Therapy in Coronavirus Disease COVID-19 Patients

MP3-pulses-COVID-19. Methylprednisolone Pulses Versus Dexamethasone According RECOVERY Protocol in Patients With Pneumonia Due to SARS-COV-2 Coronavirus Infection

Treatment with glucocorticoids in COVID patients. Low-intervention, phase IV, open-label, randomised, low-intervention clinical trial comparing 2 active treatments.

Study Overview

• Status: Terminated
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: Dexamethasone; Drug: Methylprednisolone

Detailed Description

The use of high-dose bolus glucocorticoids in the treatment of patients with COVID-19 infection will increase the anti-inflammatory effect without increasing side effects. This will allow a better patient outcome, reducing the number of deaths and the need for intubation or admission to the Intensive Care Unit.

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • León, Spain, 24071
    • Complejo Asistencial Universitario de León
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca
  • Valladolid, Spain, 47012
    • Hospital Universitario Río Hortega
  • Valladolid, Spain, 47003
    • Hospital Clinico Universitario de Valladolid

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. Over 18 years of age
2. Inpatient
3. Diagnosis of SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or antigen
4. They present evidence in computerized axial tomography (CT) of pulmonary involvement attributed to the infection by COVID. Patients in whom CT scans are not performed must have suspected pulmonary involvement by clinical examination with simple compatible or suggestive radiology.
5. Requires supplementary oxygen due to basal saturation ≤ 93% (with ambient O2, 21%)

Exclusion Criteria:

1. The patient's situation is so serious that the doctor in charge thinks he could die within 24 hours.

2. At the time of randomisation, patients require one of the following 4 ventilatory supports:

   1. high-flow oxygen devices.
   2. non-invasive mechanical ventilation.
   3. invasive mechanical ventilation.
   4. Extracorporeal membrane oxygenation (ECMO).
3. The patient is or has been treated in the 2 weeks prior to randomisation with glucocorticoids or inflammation modifying drugs, both conventional (thiopurines, cyclophosphamide, cyclosporine, tacrolimus), leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, sulfasalazine, hydroxychloroquine or chloroquine) as synthetics or biologics directed against therapeutic targets (abatacept, belimumab, CD-20, IL1, IL6, Il12. 23, IL-23, Il.17, TNF, integrin α4β7 or Janus kinase inhibitors JAK). Patients who are only on maintenance treatment with doses of steroids less than or equal to 7.5 mg of prednisone or equivalent per day will not be excluded.
4. The patient is pregnant or breastfeeding.
5. The patient has a chronic renal disease is stage 4 or 5 (CCr <30 ml/min).
6. Moderate to severe dementia at the investigator's discretion.
7. Hypersensitivity to any of the active ingredients or to any of the excipients included in its formulation.
8. Untreated systemic infections not caused by COVID-19.
9. Active stomach or duodenal ulcer.
10. Recent vaccination with live vaccines.
11. Other infection or disease that explains the lung disorder.
12. Inability of the patient to understand the study or to sign the informed consent unless consent is delegated to a legal representative.
13. Active participation in another clinical study in the last 15 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RECOVERY; intermediate-dose dexamethasone (6mg/24h - 10 days)	Drug: Dexamethasone; 6 mg/24h - 10 days; Other Names: Recovery
Experimental: BOLUS; high-dose methylprednisolone bolus (250mg/4h - 3 days)	Drug: Methylprednisolone; 250 mg/ 24h - 3 days; Other Names: Bolus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate in COVID-19 patients after high-dose methylprednisolone bolus administration versus mortality rate intermediate-dose dexamethasone pattern (RECOVERY trial)	Mortality rate (percentage)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Admission in Intensive Unit Care (ICU)	Incidence of ICU admission	28 days
Evaluation of respiratory support requirements	Proportion of patients (number of cases with respiratory support requirement / total number of patients) with non-invasive mechanical ventilation and/or high-flow oxygen requirements.; Proportion of patients (number of cases with respiratory support requirement / total number of patients) with invasive mechanical ventilation or intubation requirements.	28 days
Days in hospital	Number of days in hospital from the star of the treatment until discharge	28 days
Evaluation of presence of adverse events related with use of high dose of glucocorticoids.	Presence or absence of adverse effects (infections, hyperglycaemia, psychotic states or other adverse effects).; Incidence of infections, hyperglycaemia, psychotic states or other adverse effects, if applicable	28 days
Evaluation of other immunosuppressors requirements.	Occurrence of use of other immunosuppressors (active substance, dose, duration, if applicable)	28 days
Status according to the World Health Organization (WHO) 10-category scale.	Clinical evaluation of patient status according to the WHO 10-category scale.	3 months

Collaborators and Investigators

• Sponsor: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• Collaborators: Instituto de Investigación Biomédica de Salamanca
• Investigators: Principal Investigator: Luis Corral Gudino, Investigator

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): November 9, 2021

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Coronavirus Infections; Infections; 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; Dexamethasone; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: MP3-pulses-COVID-19; 2020-005026-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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