Clinical trial NCT04359511: Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia
Official title: Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia in Grand Ouest Interregion France
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.
timeFrame: 14 days
Secondary outcomes:
measure: Proportion of patients free of oxygen at day 14 and 28
timeFrame: 14 and 28 days
measure: Proportion of patients discharged alive from hospital at day 14 and 28
timeFrame: 14 and 28 days
measure: Time to discharge for patients alive
timeFrame: 28 days
measure: Proportion of patients that were hospitalized to ICU or who died at day 14 and 28
timeFrame: 14 and 28 days
measure: 14 and 28 day mortality rate
timeFrame: 14 and 28 days
measure: The time until weaning from oxygen therapy
timeFrame: 28 days
measure: The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28
timeFrame: 14 and 28 days
Other outcomes:
Locations:
Study officials:
affiliation: CHRU DE TOURS
name: LOUIS BERNARD, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: JOUNEAU STEPHANE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU DE TOURS
name: MAILLOT FRANCOIS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH DE BLOIS
name: LIOGER BERTRAND, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Le Mans
name: GOUPIL FRANCOIS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH DE CHARTRES
name: RABUT Thi- Tuyet Hong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH DE RDREUX
name: POPA Mihai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHR ORLEANS
name: MOREL HUGUES, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH DE VANNES
name: GUY TIPHAINE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH AMBOISE
name: LEMMENS BRUNO, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH SAINT MALO
name: BAZIN YANN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH DE CHATEAUROUX
name: ROY XAVIER, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH DE BOURGES
name: PECQUERIAUX OLIVIER, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU DE TOURS
name: MARCHAND ADAM Sylvain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: