Corticosteroids During Covid-19 Viral Pneumonia Related to SARS-Cov-2 Infection (CORTI-Covid)

Infection with the SARS-Cov-2 virus, responsible of severe acute respiratory distress syndrome (SARS), is an emerging infectious disease called Covid-19 and declared as pandemic by the World Health Organization on March 11, 2020. This pandemic is responsible of significant mortality. In France, several thousand patients are hospitalized in intensive care units, and their number continues to increase. Mortality during Covid-19 is mainly linked to acute respiratory distress syndrome, which frequency is estimated in France to occur in 6% of infected patients. Comorbidities such as cardiovascular conditions, obesity and diabetes increase susceptibility to severe forms of Covid-19 and associated mortality. Therapeutic management has three components: symptomatic management, including supplementary oxygen therapy and in case of respiratory distress mechanical ventilation; the antiviral approach; and immunomodulation, aiming at reducing inflammation associated with viral infection, which is considered to take part in severe presentations of the disease.

During Covid-19 viral pneumonia related to SARS-COv-2, there is a significant release of pro-inflammatory cytokines in the acute phase of viral infection, which could participate in viral pneumonia lesions. In children with less mature immune system than adults, SARS-Cov-2 infection is less severe. The current prevailing assumption is that severe forms of Covid-19 may not only be related to high viral replication, but also to an excessive inflammatory response favoring acute lung injury and stimulating infection.

The investigators hypothesize that early control of the excessive inflammatory response may help reducing the risk of acute respiratory distress syndrome.

The investigators will evaluate the benefit, safety and tolerability of corticosteroid therapy to reduce the rate of subjects hospitalized for Covid-19 viral pneumonia who experience clinical worsening with a need of high-flow supplemental oxygen supplementation or transfer in intensive care units for respiratory support.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Viral Pneumonia Human Coronavirus
• Intervention / Treatment: Drug: Prednisone; Other: Control group

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bron, France
    • Hôpital Pneumologique et Cardiovasculaire Louis Pradel
  • Lyon, France
    • Hôpital Edouard Herriot
  • Lyon, France
    • Groupement Hospitalier Nord
  • Lyon, France
    • Hôpital St Joseph Saint Luc
  • Marseille, France
    • Hôpital St Joseph
  • Pierre-Bénite, France
    • Centre Hospitalier Lyon Sud
  • Saint-Étienne, France
    • CHU St Etienne
  • Sainte-Foy-lès-Lyon, France
    • Clinique Charcot
  • Vienne, France
    • CHG Vienne
  • Villeurbanne, France
    • Medipole
  • Vénissieux, France
    • Clinique des Portes du Sud
  • Épagny, France
    • CH Annecy-Genevois

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:

• Age ≥ 18 years old,
• Hospitalization for COVID-19 infection confirmed by RT-PCR or other virological method,
• Peripheral saturation by pulse oximeter SpO2 ≤ 94% in ambient air measured twice at 5-15 min intervals, or PaO2 / FiO2 <300 mmHg,
• Abnormalities on the chest x-ray or CT scan suggestive of viral pneumonia,
• Signed informed consent by the patient.

Exclusion Criteria:

• Covid-19 infection with first symptoms lasting for more than 9 days according to the patient's interview; D1 of symptoms is defined by the first day with fever, cough, shortness of breath, and / or chills related to Covid-19 infection;
• Patients with primary or secondary immune deficiency, including: HIV, chronic hematological disease, solid organ transplant, ongoing immunosuppressive therapy,
• Long-term corticosteroid therapy defined by a prescription of more than 10 mg/d (prednisone equivalent),
• Suspected or confirmed infection with bacteria, fungal agents or viruses (in addition to Covid-19),
• Known contraindication to systemic corticosteroids,
• Systolic blood pressure <80 mmHg,
• SpO2 <90% under 5 L / min of oxygen using medium concentration mask, or higher oxygen requirements,
• Patient on long-term oxygen therapy,
• Ongoing mechanical ventilation,
• Ongoing septic shock ongoing,
• Ongoing multi-organ failure ongoing,
• Participating in other COVID-19 therapeutic clinical trial
• Pregnant or breast-feeding woman (oral diagnosis),
• No affiliation or beneficiary of health insurance,

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
Other: Control group	Other: Control group; The control group will receive standard of care according to the international recommendations and practices of the investigational site. No corticosteroid therapy can be prescribed in this group.
Experimental: Prednisone group; Prednisone during 10 days after randomization	Drug: Prednisone; The experimental group will receive oral prednisone during 10 days (0.75 mg/kg/day during 5 days then 20 mg/day during 5 more days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with a theoretical respiratory indication for transfer to intensive care unit evaluated by a SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask.	SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask. measured twice at 5-15 min intervalsThe average value of the two measurements will be calculated.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease severity assessed on a 7-level ordinal scale	level1: not hospitalized no limited activities, level 7: death	7 days
number of patients with a supplemental oxygen use		7 days
radiological signs on chest imaging	Reduction of radiological signs on chest imaging	7 days
number of patients transferred to intensive care unit		21 days
number of patients requiring invasive ventilation		21 days
Duration of oxygen therapy	duration on days	21 days
number of adverse events induced by corticosteroid treatment		21 days
number of patients with infections other than SARS-CoV-2		21 days
number of deaths		21 days

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Jean-François MORNEX, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2020
• Primary Completion (Actual): August 18, 2020
• Study Completion (Actual): August 18, 2020

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: COVID 19; Prednisone; SARS-Cov-2; Pneumology; viral pneumology
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Pneumonia; Pneumonia, Viral; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 69HCL20_0321; 2020-001553-48 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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