Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 Pneumonia

NCT04344730 | Unknown DMC

• 2 other identifiers: APHP2003882020-001457-43
• Study Type: interventional
• Target: 550
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Hypoxemic Respiratory Failure; COVID-19

Keywords

COVID-19; acute hypoxemic respiratory failure (AHRF)

Outcome Measures

Primary Outcomes (2)

• 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.

Secondary Outcomes (10)

• The viral load in the respiratory tract

  day-10

• Number of patient with at least one episode of healthcare-associated infections

  day-28

• Number of days alive without mechanical ventilation

  day-28

• Measure of SOFA score

  day-1 to day 3, day 7, day 10, day 21, day 28

• Number of days alive without renal replacement therapy

  day-28

Study Arms (8)

Standard oxygen 1

PLACEBO COMPARATOR

Standard oxygen and placebo of Dexamethasone

Drug: placebo; Procedure: conventional oxygen

Standard oxygen 2

EXPERIMENTAL

Standard oxygen and Dexamethasone

Drug: Dexamethasone injection; Procedure: conventional oxygen

CPAP 1

EXPERIMENTAL

CPAP and placebo of Dexamethasone

Drug: placebo; Procedure: CPAP

CPAP 2

EXPERIMENTAL

CPAP and Dexamethasone

Drug: Dexamethasone injection; Procedure: CPAP

HFNO 1

EXPERIMENTAL

HFNO and placebo of Dexamethasone

Drug: placebo; Procedure: HFNO

HFNO 2

EXPERIMENTAL

HFNO and Dexamethasone

Drug: Dexamethasone injection; Procedure: HFNO

mechanically ventilated 1

PLACEBO COMPARATOR

placebo

Drug: placebo; Procedure: mechanical ventilation

mechanically ventilated 2

EXPERIMENTAL

Dexamethasone

Drug: Dexamethasone injection; Procedure: mechanical ventilation

Interventions

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.

Also known as: experimental treatment

CPAP 2; HFNO 2; Standard oxygen 2; mechanically ventilated 2

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.

CPAP 1; HFNO 1; Standard oxygen 1; mechanically ventilated 1

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)

Standard oxygen 1; Standard oxygen 2

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)

CPAP 1; CPAP 2

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

HFNO 1; HFNO 2

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)

mechanically ventilated 1; mechanically ventilated 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Admitted to ICU within 48 hours
• Confirmed or highly suspected COVID-19 infection
• Acute hypoxemic respiratory failure (PaO2 \<70 mmHg or SpO2\<90% on room air or tachypnea\>30/min or labored breathing or respiratory distress; need for oxygen flow \>=6L/min)
• Any treatment intended to treat the SARS-CoV-2 infection in the absence of contraindications (either as a compassionate use or in the context of a clinical trial, i.e remdesivir, lopinavir/ritonavir, favipiravir, hydroxychloroquine and any other new drug with potential activity).
• Moribund status
• Pregnancy or breastfeeding
• Long term corticotherapy at a dose of 0.5mg/kg/j or higher
• Active and untreated bacterial, fungal or parasitic infection
• Not Written informed consent from the patient or a legal representative if appropriate . If absence a legal representative the patient may be included in emergency procedure
• hypersensitivity to dexamethasone or to any of the excipients
• Not Affiliation to the French social security

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Bichat - Aphp

Paris, 75018, France

Location

Related Publications (3)

• 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.

  PMID: 37634234 DERIVED

• 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.

  PMID: 36522698 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.

  PMID: 35788622 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency; COVID-19

Interventions

Calcium Dobesilate; Respiration, Artificial

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Airway Management; Therapeutics; Resuscitation; Emergency Treatment; Respiratory Therapy

Study Officials

• Jean François TIMSIT, Pr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The masking label is available only for the treatment assignation
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: April 10, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 9, 2021

Record last verified: 2021-02

Locations

FR (1)