Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia

NCT ID: NCT04359511

Last Updated: 2021-05-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-03
• Study Completion Date: 2020-07-03

Brief Summary

To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD).

We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.

Detailed Description

"Severe acute respiratory syndrome" coronavirus 2 (SARS-Cov-2) is a new coronavirus that induces pneumonia called Corona Virus Disease- 19 (COVID-19), an infected 1.5 million people worldwide and caused the more than 85,000 patients died. COVID-19 usually comes in the form of viral pneumonia but with the peculiarities of a risk frequent worsening towards acute respiratory distress syndrome (ARDS) and a usual duration of oxygen dependence in fragile patients by their age or their comorbidities. To date, there is no therapy effective in preventing or treating COVID-19. Drug identification is a major concern and a public health emergency. Retrospective study (Wu 2020) highlighted improved survival in COVID-19 patients with acute ARDS and treated with corticosteroids (CS). So even in the absence of evidence of effectiveness, the SCs are used for COVID-19 oxygen-dependent patients or with an ARDS. However, their benefit / risk remains debated (Russel 2020). On histological samples of COVID-19, diffuse alveolar damage (DAD) has been especially observed (Hanley 2020). DAD is described histologically in an exudative phase, an organizational phase and a irreversible fibrotic phase (Hughes 2017). SC could have an effect beneficial by limiting the exudative / inflammatory phase but also that organization whose histological and CT aspects are sometimes indistinguishable from organized pneumonia, a form of pulmonary repair aberrant very corticosensitive (Travis 2013). Chest scans performed in the face of the persistence or worsening of oxygen dependence beyond the 7th day of COVID-19 symptoms, could help discern indirect complications (pulmonary embolism, exacerbation of COPD, bacterial superinfection, etc.) of an unfavorable course COVID-19 (by displaying an aspect suggesting DAD in particular during the organization phase). We hypothesize that, in the context of COVID-19, the SCs may be beneficial in patients with CT scans thoracic images suggestive of DAD either at the exudative phase or at the pulmonary organization phase.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

corticosteroid + Optimized Standard of Care

• prednisone 0.7 mg/kg/day for 10 days, administered orally, once a day, or
• hydrocortisone hemisuccinate 3.5 mg/kg/day by continuous infusion for 10 days, administered by IV route if the patient cannot take drugs by oral route,

• standard of care

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

prednisone 0.7 mg/kg/d (PO)

Hydrocortisone

Intervention Type: DRUG

hémisuccinate d'hydrocortisone 3,5 mg/kg/jour (IV)

Optimized Standard of Care

standard of care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Prednisone

prednisone 0.7 mg/kg/d (PO)

Intervention Type: DRUG

Hydrocortisone

hémisuccinate d'hydrocortisone 3,5 mg/kg/jour (IV)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients ≥ 18 years old,
• Hospitalized with a proven diagnosis of COVID-19 (SARS-CoV-2 positive in RTPCR), in medicine or in intensive care.
• With a need for oxygen therapy ≥ 2 l / min to maintain a Sp02> 92% or a need for oxygen therapy to maintain a PaO2 / FiO2> 300 mmHg (for intubated patients).
• With a chest scanner at least 7 days after the onset of symptoms, and whose centralized interpretation shows a CT scan aspect suggestive of intense and predominant DAD which can explain the patient's oxygen dependence.
• Signature of a free, written and informed consent by the patient, or the person of trust
• Affiliate or beneficiary of a social security scheme.

Exclusion Criteria

• Patients already treated by CS for a chronic disease.
• Patients with a known contraindication to SC, such as hypersensitivity.
• Patients at risk of dying within 48 hours.
• Pregnant or breastfeeding women.
• Patients under guardianship, curatorship, safeguard of justice.
• Poor understanding of the French language.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

LOUIS BERNARD, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU DE TOURS

JOUNEAU STEPHANE, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

MAILLOT FRANCOIS, MD

Role: PRINCIPAL_INVESTIGATOR

CHRU DE TOURS

LIOGER BERTRAND, MD

Role: PRINCIPAL_INVESTIGATOR

CH DE BLOIS

GOUPIL FRANCOIS, MD

Role: PRINCIPAL_INVESTIGATOR

CH Le Mans

RABUT Thi- Tuyet Hong, MD

Role: PRINCIPAL_INVESTIGATOR

CH DE CHARTRES

POPA Mihai, MD

Role: PRINCIPAL_INVESTIGATOR

CH DE RDREUX

MOREL HUGUES, MD

Role: PRINCIPAL_INVESTIGATOR

CHR ORLEANS

GUY TIPHAINE, MD

Role: PRINCIPAL_INVESTIGATOR

CH DE VANNES

LEMMENS BRUNO, MD

Role: PRINCIPAL_INVESTIGATOR

CH AMBOISE

BAZIN YANN, MD

Role: PRINCIPAL_INVESTIGATOR

CH SAINT MALO

ROY XAVIER, MD

Role: PRINCIPAL_INVESTIGATOR

CH DE CHATEAUROUX

PECQUERIAUX OLIVIER, MD

Role: PRINCIPAL_INVESTIGATOR

CH DE BOURGES

MARCHAND ADAM Sylvain, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU DE TOURS

Other Identifiers

CORTI-COVID-19-HUGO

Identifier Type: -

Identifier Source: org_study_id

DR200136

Identifier Type: REGISTRY

Identifier Source: secondary_id