Respiratory Distress Syndrome, AdultPhase 3DHYSCONCT04347980
Dexamethasone Treatment for Severe Acute Respiratory Distress Syndrome Induced by COVID-19
A Phase 3 study testing Dexamethasone and Hydroxychloroquine and Hydroxychloroquine in people with Respiratory Distress Syndrome, Adult and COVID-19, run by Centre Chirurgical Marie Lannelongue at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Respiratory Distress Syndrome, Adult, COVID-19
- What is being tested?
- Dexamethasone and Hydroxychloroquine and Hydroxychloroquine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- 17 Apr 2020to 7 Aug 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Reanimation adulte. Hopital Marie Lannelongue
Le Plessis-Robinson, 92350
About this study
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
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.
Read the detailed description
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.
In summary:
- 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
- Conditions
- Respiratory Distress Syndrome, Adult, COVID-19
- Being tested
- Dexamethasone and Hydroxychloroquine, Hydroxychloroquine
- Keywords
- Acute Respiratory Distress Syndrome, COVID-19, Dexamethasone, Hydroxychloroquine, Mortality
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone and HydroxychloroquineDrug
Also called Standard ventilatory management
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 called Standard ventilatory management
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day-28 mortality
Mortality rate evaluated 28 days after randomization
Measured: 28 days after randomization
Secondary outcomes (5)
Ventilator-free days
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.
Measured: 28 days after randomization
Intensive Care Unit mortality
Mortality rate evaluated during Intensive care unit stay
Measured: Up to 60 days after randomization
Day-60 mortality
Mortality rate evaluated 60 days after randomization
Measured: 60 days after randomization
Nosocomial pneumonia
Number of patients with pneumonia diagnosed during intensive care unit stay
Measured: Up to 60 days after randomization
Bacteremia
Number of patients with bacteremia diagnosed during intensive care unit
Measured: Up to 60 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
- Study start17 Apr 2020
- Primary completion7 Aug 2020
- Study completion7 Aug 2020
Why it stopped: ANSM RECOMMANDATION
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Distress Syndrome, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Chirurgical Marie Lannelongue
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francois STEPHAN, MD, PhD, Principal investigator, Centre Chirurgical Marie Lannelongue
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04347980
- Sponsor's protocol ID
- 2037815010
- Acronym
- DHYSCO
- Status last verified
- Aug 2021
- First submitted
- 9 Apr 2020
- Last updated
- 12 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04347980
- Acronym / sponsor ID
- DHYSCO / 2037815010
- Conditions
- Respiratory Distress Syndrome, Adult, COVID-19
- Keywords
- Acute Respiratory Distress Syndrome, COVID-19, Dexamethasone, Hydroxychloroquine, Mortality
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: ANSM RECOMMANDATION
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Centre Chirurgical Marie LannelongueUniversity, hospital or other
- Study start
- 17 Apr 2020 (actual)
- Primary completion
- 7 Aug 2020 (actual)
- Study completion
- 7 Aug 2020 (actual)
- First posted
- 15 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
In summary:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone and Hydroxychloroquine (HCQ/DXM) | Experimental | Drug: Dexamethasone and HydroxychloroquinePatients 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. |
| Hydroxychloroquine (HCQ) | Active comparator | Drug: HydroxychloroquinePatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexamethasone and HydroxychloroquineAlso: Standard ventilatory managementPatients 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. | Drug | Dexamethasone and Hydroxychloroquine (HCQ/DXM) |
| HydroxychloroquineAlso: Standard ventilatory managementPatients 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. | Drug | Hydroxychloroquine (HCQ) |
Primary outcome
Day-28 mortality
Time frame: 28 days after randomization
Mortality rate evaluated 28 days after randomization
5 secondary outcomes
Ventilator-free days
Time frame: 28 days after randomization
Intensive Care Unit mortality
Time frame: Up to 60 days after randomization
Day-60 mortality
Time frame: 60 days after randomization
Nosocomial pneumonia
Time frame: Up to 60 days after randomization
Bacteremia
Time frame: Up to 60 days after randomization
Results and safety
The study was stopped early (reason given: ANSM RECOMMANDATION). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2021.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francois STEPHAN, MD, PhD principal investigator
Centre Chirurgical Marie Lannelongue
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone and Hydroxychloroquine and Hydroxychloroquine in people with Respiratory Distress Syndrome, Adult and COVID-19, run by Centre Chirurgical Marie Lannelongue at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: ANSM RECOMMANDATION). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Day-28 mortality (time frame: 28 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2021.