Dexamethasone Treatment for Severe Acute Respiratory Distress Syndrome Induced by COVID-19

NCT04347980 | Terminated Phase 3 DMC

• 1 other identifier: 2037815010
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Single blind randomized clinical trial designed to evaluate the efficacy of the combination of hydroxychloroquine and dexamethasone as treatment for severe Acute Respiratory Distress Syndrome (ARDS) related to coronavirus disease 19 (COVID-19). We hypothesize that dexamethasone (20 mg for 5 days followed by 10 mg for 5 days) combined with 600 mg per day dose of hydroxychloroquine for 10 days will reduce the 28-day mortality compared to hydroxychloroquine alone in patients with severe ARDS related COVID-19.

Conditions

Respiratory Distress Syndrome, Adult; COVID-19

Keywords

Acute Respiratory Distress Syndrome; COVID-19; Dexamethasone; Hydroxychloroquine; Mortality

Outcome Measures

Primary Outcomes (1)

• Day-28 mortality

  Mortality rate evaluated 28 days after randomization

  28 days after randomization

Secondary Outcomes (5)

• Ventilator-free days

  28 days after randomization

• Intensive Care Unit mortality

  Up to 60 days after randomization

• Day-60 mortality

  60 days after randomization

• Nosocomial pneumonia

  Up to 60 days after randomization

• Bacteremia

  Up to 60 days after randomization

Other Outcomes (3)

• Extra corporeal membrane oxygenation (ECMO)

  Up to 60days after randomization

• Tracheostomy

  Up to 60 days after randomization

• Prone Position

  Up to 60 days after randomization

Study Arms (2)

Dexamethasone and Hydroxychloroquine (HCQ/DXM)

EXPERIMENTAL

Patients included in the "HCQ / DXM" group will benefit from standardized ventilatory management and administration of HCQ in the same manner as the "HCQ" group. They will receive in addition to DXM at a rate of 20 mg intravenously for 15 min once a day for 5 days (D1 to D5) then at a rate of 10 mg per day from D6 to D10. If the patient is extubated before the 10th day, he will receive his last dose of DXM before.

Drug: Dexamethasone and Hydroxychloroquine

Hydroxychloroquine (HCQ)

ACTIVE COMPARATOR

Patients included in the "HCQ " group will benefit from standardized ventilatory management. Patients included in the "HCQ" group will receive 200 mg x 3 / day enterally from J1 of the HCQ for 10 days. If the patient is extubated before the 10th day, he will receive his last dose of HCQ before.

Drug: Hydroxychloroquine

Interventions

Dexamethasone and Hydroxychloroquine DRUG

Patients included in the "Hydroxychloroquine / Dexamethasone" group will benefit from standardized ventilatory management and administration of Hydroxychloroquine in the same manner as the Hydroxychloroquine group. They will receive in addition to Dexamethasone at a rate of 20 mg intravenously for 15 min once a day for 5 days (D1 to D5) then at a rate of 10 mg per day from D6 to D10. If the patient is extubated before the 10th day, he will receive his last dose of Dexamethasone before.

Also known as: Standard ventilatory management

Dexamethasone and Hydroxychloroquine (HCQ/DXM)

Hydroxychloroquine DRUG

Patients included in the Hydroxychloroquine group will benefit from standardized ventilatory management. Patients included in the Hydroxychloroquine group will receive 200 mg x 3 / day enterally from J1 of the HCQ for 10 days. If the patient is extubated before the 10th day, he will receive his last dose of HCQ before.

Also known as: Standard ventilatory management

Hydroxychloroquine (HCQ)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient over 18 years old
• Patient affiliated to a health insurance plan
• Patient who has given their free, informed and written consent or patient for whom an independent doctor has given their signed consent as part of an emergency procedure
• Kaliemia \> 3,5 mmol / L
• Patient diagnosed COVID-19 positive by reverse transcription-polymerase chain reaction (RT-PCR) and / or CT
• The diagnosis of COVID-19 will be made if:
• Patient with radiological images strongly suggestive of a chest scan associated with respiratory symptoms, without other obvious etiologies OR
• Patient with suggestive respiratory symptoms associated with a positive RT-PCR
• Patients admitted to intensive care with acute respiratory distress syndrome secondary to COVID-19, intubated for less than 5 days with:
• Either - Hypoxemia defined by a arterial partial pressure of oxygen / fraction of inspiratory oxygen ratio (PaO2 / FiO2) ratio \<100 after 2 sessions of prone position
• Either - An alteration in pulmonary compliance (tidal volume divided by plateau pressure minus positive expiratory pressure) immediately or over the first 96 hours after the start of ARDS defined by:
• immediately: impossibility of maintaining a plateau pressure \<30 cm of water in a ventilated patient with a tidal volume of 6 ml / kg of weight predicted by the size and a positive expiratory pressure at 10 cm of water
• during the course of the evolution: decrease in compliance by 20% compared to the initial compliance (day of treatment of the intubated and ventilated patient) We define the start date of ARDS by the day and time when the patient is intubated and ventilated with regard to our definition of COVID-19

You may not qualify if:

• Patient under guardianship or curator
• Patient with plausible alternate diagnosis
• ARDS evolving for more than 4 days
• Contraindication to the Hydroxychloroquine : Known allergy or intolerance to the Hydroxychloroquine or to one of the excipients of the drug, in particular to lactose; documented QT prolongation and / or known risk factors for QT prolongation (including ongoing treatment with citalopram, escitalopram, hydroxyzine, domperidone or piperaquine), retinopathies
• Contraindication to Dexamethasone: Known allergy or intolerance to Dexamethasone or to one of the excipients of the drug, another evolving virosis (hepatitis, herpes, chickenpox, shingles), severe coagulation disorder
• Uncontrolled septic shock
• Untreated active infection or treated less than 24 hours
• Long-term patient treated with corticosteroids (\> 20 mg / day) or Hydroxychloroquine
• Immunocompromised patients: AIDS, bone marrow or solid organ transplant recipients
• Pregnant women
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Sponsors & Collaborators

• Centre Chirurgical Marie Lannelongue: lead

Study Sites (1)

Reanimation adulte. Hopital Marie Lannelongue

Le Plessis-Robinson, 92350, France

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19

Interventions

Dexamethasone; Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Francois STEPHAN, MD, PhD

  Centre Chirurgical Marie Lannelongue

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 15, 2020
• Study Start: April 17, 2020
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: August 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 24 months following article publication
• Access Criteria: Researchers who provide a methodologically sound and proposal. Data are available for 24 months and request should be addressed by email

Locations

FR (1)