Dexamethasone Treatment for Severe Acute Respiratory Distress Syndrome Induced by COVID-19 (DHYSCO)
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|ClinicalTrials.gov Identifier: NCT04347980|
Recruitment Status : Recruiting
First Posted : April 15, 2020
Last Update Posted : April 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Respiratory Distress Syndrome, Adult COVID-19||Drug: Dexamethasone and Hydroxychloroquine Drug: Hydroxychloroquine||Phase 3|
The severe acute respiratory syndrome coronavirus 2 pandemic causing COVID-19 disease affects hundreds of thousands of patients. Of these, 5% will present with acute respiratory failure, the most severe form of which is Acute Respiratory Distress Syndrome (ARDS). Hospital mortality affects 45% of patients with severe ARDS. The improvement in mortality associated with ARDS seems largely explained by the reduction in lesions induced by mechanical ventilation, in particular a tidal volume (Vt) set at 6 ml / kg of the weight predicted by the size associated with a plateau pressure must not exceed 30 cm of water. Unfortunately and despite the application of these recommendations, ARDS related COVID-19 is associated with a mortality of 65%. About 42% of patients hospitalized for COVID-19 pneumonitis will develop ARDS and the onset of ARDS is rapid after admission with a median of 2 days. Interestingly, a study reported that patients suffering from ARDS and having received corticosteroids had a mortality rate of 46% (23 out of 50) compared to 61.8% (21 out of 34) in patients who did not receive corticosteroids. However, this difference was not significant (P = 0.15). The survival curve showed, however, that the administration of corticosteroids (Methylprednisolone) reduced the risk of death (Hazard ratio: 0.38 (95% confidence interval 0.20-0.72); P = 0.003). The authors concluded that a randomized study was necessary to confirm this impression.
The theoretical justification for treatment with corticosteroids is related to the recognition of the inflammatory syndrome as a factor in the development of an uncontrolled and harmful fibroproliferative phase. It seems certain that late administration (beyond the 14th day after the start of ARDS) is deleterious in patients by increasing mortality. However, a recent study shows that early administration of dexamethasone (within 30 hours after the start of ARDS) is associated with an increase of ventilator-free days and a decrease in mortality at 2 months.
In COVID-19 disease, there is also a cytokine storm and an intense inflammatory reaction. Currently the use of corticosteroids is not recommended during a severe acute respiratory syndrome coronavirus 2 infection. Administration of corticosteroids may delay elimination of the virus. Recently, a preliminary study reported that the administration of hydroxychloroquine (200mg x3 per day) decreased or even made disappear the viral load. This clinical study appears to corroborate an experimental study. However, hydroxychloroquine can have cardiac toxicity which, although rare, can be serious.
- The appearance of an ARDS during a COVID-19 is burdened with a mortality of 65%
- The viral load has decreased when ARDS is present
- The use of hydroxychloroquine makes it possible to significantly reduce the viral load
- Early administration of corticosteroids seems beneficial in ARDS
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||122 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Dexamethasone Combined With Hydroxychloroquine Compared to Hydroxychloroquine Alone for Treatment of Severe Acute Respiratory Distress Syndrome Induced by Coronavirus Disease 19 (COVID-19): a Multicentre, Randomised Controlled Trial|
|Estimated Study Start Date :||April 2020|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||August 2020|
Experimental: Dexamethasone and Hydroxychloroquine (HCQ/DXM)
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
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.
Other Name: Standard ventilatory management
Active Comparator: Hydroxychloroquine (HCQ)
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.
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.
Other Name: Standard ventilatory management
- Day-28 mortality [ Time Frame: 28 days after randomization ]Mortality rate evaluated 28 days after randomization
- Ventilator-free days [ Time Frame: 28 days after randomization ]
Ventilator-free days (VFDs) at 28 days are one of several organ failure-free outcome measures to quantify the efficacy of therapies and interventions. VFDs are typically defined as follows:
- VFDs = 0 if subject dies within 28 days of mechanical ventilation.
- VFDs = 28 - x if successfully liberated from ventilation x days after initiation.
- VFDs = 0 if the subject is mechanically ventilated for >28 days.
- Intensive Care Unit mortality [ Time Frame: Up to 60 days after randomization ]Mortality rate evaluated during Intensive care unit stay
- Day-60 mortality [ Time Frame: 60 days after randomization ]Mortality rate evaluated 60 days after randomization
- Nosocomial pneumonia [ Time Frame: Up to 60 days after randomization ]Number of patients with pneumonia diagnosed during intensive care unit stay
- Bacteremia [ Time Frame: Up to 60 days after randomization ]Number of patients with bacteremia diagnosed during intensive care unit
- Extra corporeal membrane oxygenation (ECMO) [ Time Frame: Up to 60days after randomization ]Placement of ECMO during intensive care unit stay
- Tracheostomy [ Time Frame: Up to 60 days after randomization ]Number of patients who underwent tracheostomy during intensive care unit stay
- Prone Position [ Time Frame: Up to 60 days after randomization ]Number of Prone position session
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04347980
|Contact: Francois STEPHAN, MD, PhDfirstname.lastname@example.org|
|Contact: Lilia Lamraniemail@example.com|
|Reanimation adulte. Hopital Marie Lannelongue||Recruiting|
|Le Plessis-Robinson, France, 92350|
|Contact: Francois STEPHAN, MD, PhD 0140948580 firstname.lastname@example.org|
|Principal Investigator: Francois STEPHAN, MD, PhD|
|Principal Investigator:||Francois STEPHAN, MD, PhD||Centre Chirurgical Marie Lannelongue|