Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001457-43 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality.
Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival.
The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality.
Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival.
The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
The main objective is to assess the impact of dexamethasone on overall mortality at day-60 after randomization in patients admitted in ICU for severe COVID-19 infection.
In non mechanical ventilation (MV) patients, the additional objective is to assess whether oxygen support based on either HFNO or CPAP modality in COVID-19 related AHRF reduces the need for mechanical ventilation at day-28.
An ancillary study CACAO (COVIDICUS air contamination) will be performed in 4 centers aiming at assessing the environmental contamination by SARS-CoV-2 according to the oxygen support modality. Additional funding will be searched for these analyses (submitted for ANR call).
A metanalysis on individual data will be performed using patients enrolled in the 3 PHRC flash exploring the activity of corticosteroids.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard oxygen 1 | Placebo Comparator | Standard oxygen and placebo of Dexamethasone |
|
| Standard oxygen 2 | Experimental | Standard oxygen and Dexamethasone |
|
| CPAP 1 | Experimental | CPAP and placebo of Dexamethasone |
|
| CPAP 2 | Experimental | CPAP and Dexamethasone |
|
| HFNO 1 | Experimental | HFNO and placebo of Dexamethasone |
|
| HFNO 2 | Experimental | HFNO and Dexamethasone |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamethasone injection | Drug | Box of 10 DEXAMETHASONE 20 mg / 5 ml, solution for injection in ampoule of 5mL. Each allocated box contains complete treatment from D1 to D10 for one patient. |
| Measure | Description | Time Frame |
|---|---|---|
| The time-to-death from all causes | The time-to-death from all causes within the first 60 days after randomization. | day-60 |
| The time to need for mechanical ventilation (MV) | the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization. | day-28. |
| Measure | Description | Time Frame |
|---|---|---|
| The viral load in the respiratory tract | The cycle threshold for SARS-CoV-2 PCR at baseline, day 7+/-1 and day 10 +/- in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab) | day-10 |
| Number of patient with at least one episode of healthcare-associated infections |
Not provided
Inclusion Criteria:
Non-inclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jean François TIMSIT, Pr | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Bichat - Aphp | Paris | 75018 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37634234 | Derived | Chevret S, Bouadma L, Dupuis C, Burdet C, Timsit JF; COVIDICUS RCT group. Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial. Ann Intensive Care. 2023 Aug 27;13(1):75. doi: 10.1186/s13613-023-01168-z. | |
| 36522698 | Derived |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012131 | Respiratory Insufficiency |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
Not provided
Not provided
| ID | Term |
|---|---|
| D002123 | Calcium Dobesilate |
| D012121 | Respiration, Artificial |
| ID | Term |
|---|---|
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
Not provided
Not provided
In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.
Not provided
Not provided
The masking label is available only for the treatment assignation
|
| mechanically ventilated 1 | Placebo Comparator | placebo |
|
| mechanically ventilated 2 | Experimental | Dexamethasone |
|
|
| placebo | Drug | Box of 10 NaCl 0,9% , solution for injection in ampoule of 5mL. Each allocated box contains complete treatment from D1 to D10 for one patient. |
|
| conventional oxygen | Procedure | The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2) |
|
| CPAP | Procedure | Patients assigned to the CPAP plus oxygen group will receive periods of CPAP in addition to the standard treatment.The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2) |
|
| HFNO | Procedure | TIn the high-flow-nasal cannula group, oxygen will be delivered through a heated humidifier (Airvo-2, Fisher and Paykel Healthcare) and applied continuously through large-bore binasal prongs, with a gas flow rate of 30 liters per minute and adjusted based on the clinical response. FiO2 will be adjusted for the target SpO2 |
|
| mechanical ventilation | Procedure | The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2) |
|
Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28 |
| day-28 |
| Number of days alive without mechanical ventilation | To compare the exposition to mechanical ventilation | day-28 |
| Measure of SOFA score | Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status) | day-1 to day 3, day 7, day 10, day 21, day 28 |
| Number of days alive without renal replacement therapy | to compare the exposition to renal replacement therapy | day-28 |
| Lengths of ICU-stay | To compare the lengths of ICU | day-60 |
| Lengths of hospital-stay | To compare the lengths of hospital-stay | day-60 |
| Number of patients with severe hypoxemia, | Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation | day 60 |
| Proportion of patients with cardiac arrest within 1 hour after intubation | Proportion of patients with cardiac arrest within 1 hour after intubation | day 60 |
| Overall survival | To compare Overall survival after randomization | day 60 |
| Chevret S, Timsit JF, Biard L. Challenges of using external data in clinical trials- an illustration in patients with COVID-19. BMC Med Res Methodol. 2022 Dec 15;22(1):321. doi: 10.1186/s12874-022-01769-5. |
| 35788622 | Derived | Bouadma L, Mekontso-Dessap A, Burdet C, Merdji H, Poissy J, Dupuis C, Guitton C, Schwebel C, Cohen Y, Bruel C, Marzouk M, Geri G, Cerf C, Megarbane B, Garcon P, Kipnis E, Visseaux B, Beldjoudi N, Chevret S, Timsit JF; COVIDICUS Study Group. High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure: The COVIDICUS Randomized Clinical Trial. JAMA Intern Med. 2022 Sep 1;182(9):906-916. doi: 10.1001/jamainternmed.2022.2168. |
| D012141 |
| Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D058109 | Airway Management |
| D013812 | Therapeutics |
| D012151 | Resuscitation |
| D004638 | Emergency Treatment |
| D012138 | Respiratory Therapy |