Glucocorticoids in COVID-19 (CORTIVID) (CORTIVID)

Treatment of COVID-19 Pneumonia With Glucocorticoids. A Randomized Controlled Trial

Around 30% of admitted patients with COVID-19 pneumonia develop a hyper-inflammatory state whose progression to an acute respiratory distress syndrome (ARSD) could be prevented by the early initiation of immune-modulatory agents. The role of glucocorticoids (GC) in this setting remains controversial. This study aims to assess the safety and effectiveness of GC pulses to improve the clinical outcomes of patients with COVID-19 pneumonia with risen inflammatory biomarkers.

Study Overview

• Status: Completed
• Conditions: Covid-19 Pneumonia
• Intervention / Treatment: Drug: Methylprednisolone; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Sant Joan Despí, Barcelona, Spain
      • Hospital Sant Joan Despi Moises Broggi
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years old.
• Diagnosis of SARS-CoV-2 pneumonia confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swab or sputum according to the recommendations of the Spanish Ministry of Health.
• Length of symptoms consistent with COVID-19 ≥7 days.
• Hospital admission.
• At least one of the following: CRP >60 mg/L, IL-6 >40 pg/mL, ferritin >1000 μg/L.
• Acceptation of informed consent

Exclusion Criteria:

• Allergy or contraindication to any of the drugs under study.
• SpO2 <90% (in air ambient) or PaO2 <60 mmHg (in ambient air) or PaO2/FiO2 <300 mmHg.
• Ongoing treatment with glucocorticoids, immunosuppressive, or biologic drugs with another indication.
• Decompensated diabetes mellitus.
• Uncontrolled hypertension.
• Psychotic or manic disorder.
• Active cancer.
• Pregnancy or lactation.
• Clinical or biochemical suspicion (procalcitonin >0.5 ng/mL) of active infection other than SARS-CoV-2.
• Out-of-hospital management patient.
• Conservative or palliative management patient.
• Participation in another clinical trial.
• Any important and uncontrolled medical, psychological, psychiatric, geographic or social problem that contraindicates the patient's participation in the trial or that does not allow adequate follow-up and adherence to the protocol and evaluation of the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Methylprednisolone Arm; Standard of care plus Methylprednisolone	Drug: Methylprednisolone; -A dose of 120 mg/day of methylprednisolone for 3 days, administered by intravenous infusión
PLACEBO_COMPARATOR: Placebo Arm; Standard of care plus placebo	Other: Placebo; -An infusion bag of 100 mL of 0.9% saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients developing treatment failure	• Death	At 14 days after randomization
Proportion of patients developing treatment failure	• Need for admission in an intensive care unit (ICU)	At 14 days after randomization
Proportion of patients developing treatment failure	• Need for mechanical ventilation	At 14 days after randomization
Proportion of patients developing treatment failure	• Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment	At 14 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at day 28		At 28 days after randomization
Proportion of patients requiring ICU admission		At 28 days after randomization
Proportion of patients requiring rescue-therapy with tocilizumab		At 14 days after randomization
Length of hospital stay	Time in days from randomization until the date of hospital discharge.	At 28 days after randomization
Proportion of severe adverse events	Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant	At 28 days after randomization
Proportion of bacterial, fungal or opportunistic infections		At 28 days after randomization
Evolution of inflammatory biomarkers related to COVID-19	Change in plasma levels of C-reactive protein (CRP)	At 14 days after randomization
Evolution of inflammatory biomarkers related to COVID-19	Change in plasma levels of ferritin	At 14 days after randomization
Evolution of inflammatory biomarkers related to COVID-19	Change in plasma levels of interleukin-6 (IL-6)	At 14 days after randomization
Evolution of inflammatory biomarkers related to COVID-19	Change in plasma levels of lactate dehydrogenase (LDH)	At 14 days after randomization
Evolution of inflammatory biomarkers related to COVID-19	Change in plasma levels of D-dimer (DD)	At 14 days after randomization
Proportion of SARS-CoV-2 clearance.	Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum	At 7 days after randomization

Collaborators and Investigators

• Sponsor: Fundacion Miguel Servet
• Collaborators: Complejo Hospitalario de Navarra; Hospital Sant Joan Despí Moisès Broggi
• Investigators: Principal Investigator: Iñigo Les Bujanda, PhD, Complejo Hospitalario de Navarra

Publications and helpful links

General Publications

• Les Bujanda I, Loureiro-Amigo J, Bastons FC, Guerra IE, Sanchez JA, Murgadella-Sancho A, Rey RG, Lopez JL, Alvarez JS. Treatment of COVID-19 pneumonia with glucocorticoids (CORTIVID): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Jan 11;22(1):43. doi: 10.1186/s13063-020-04999-4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2020
• Primary Completion (ACTUAL): March 12, 2021
• Study Completion (ACTUAL): April 9, 2021

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (ACTUAL): June 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Covid-19; pneumonia; Glucocorticoids; Inflammatory phase
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; 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: CORTIVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD will be available for exploitation in future research projects. This statement also includes the availability of the study protocol, the statistical analysis plan, the informed consent form, the clinical study report and the analytic code.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No