Corona Virus Infection, Infection Viral, Virus Diseases
Conditions
Brief summary
This study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.
Detailed description
In the ongoing coronavirus pandemic, COVID-19, that arose in Wuhan China, there is still sparse data in the course, risk of various complications, and in particular how patients who are hospitalized are best treated to ensure high survival and short hospitalization. Despite the rapid spread of the disease globally, there is no solid data yet to recommend any specific treatments, which is why symptomatic, organ supportive therapy including respiratory therapy in acute pulmonary failure is recommended. There has been reported a high incidence of bacterial super-infections in patients with COVID-19. Patients with COVID-19 also have a higher risk of dying because of septic shock. Thus, there is an urgent need for treatment that can improve the patient's chance of the shortest hospitalization possible, and treatment that can lower the risk of secondary infection and death. This is a randomized, placebo-controlled, double-blinded multi-center trial evaluating the effect of azithromycin and hydroxychloroquine treatment in patients with COVID-19 during hospitalization. The aim of the study is to investigate whether the treatment can shorten hospitalization, reduce the risk of non-invasive ventilation, admittance to Intensive Care Units and death.
Interventions
DRUGAzithromycin
Azithromycin
DRUGHydroxychloroquine
Hydroxychloroquine
DRUGPlacebo oral tablet
Placebo Azithromycin
Sponsors
Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patient admitted to a Danish emergency department, lung medical department or medical department * Age \>18 years * Hospitalized \<48 hours * Positive COVID-19 test/diagnosis during the hospitalization * Signs informed consent
Exclusion criteria
* If the patient uses \> 5 LO2/min at time of recruitment * Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinolinderivates * Pregnancy * Breastfeeding * Neurogenic hearing loss * Psoriasis * Retinopathy * Maculopathy * Changes in vision field * Severe liver disease other than amoebiases * Severe gastrointestinal, neurological or haematological disorders * eGFR \< 45 ml/min/1.73m2 * Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval * Myasthenia Gravis * Uses Digoxin * Glucose-6-phosphate dehydrogenase deficiency * Porphyria * Hypoglycemia at any time since hospitalization * Severe mental illness which significantly impedes cooperation * Severe linguistic problems that significantly impedes cooperation * Treatment with sickle alkaloids
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Days Alive and Discharged From Hospital Within 14 Days | 14 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay in ICU | 14 days | Length of stay in intensive care unit. |
| Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization | 14 days | — |
| Mortality | 30 days | — |
| Length of Hospitalization | 14 days | — |
| Days Alive and Discharged From Hospital | 30 days | — |
| Categorization of Hospitalization Status | 14 days | The patient will be categorized into one of the following 8 categories depending on status of their hospitalization: 1. Dead (yes/no) 2. Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) 3. Hospitalized and receiving Non-invasive ventilation or high-flow oxygen device (yes/no) 4. Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) 5. Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) 6. Hospitalized for observation (yes/no) 7. Discharged from hospital with restriction of activity level (yes/no) 8. Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be yes. |
| Number of Days Using Non-invasive Ventilation (NIV) | 14 days | Number of days using non-invasive ventilation (NIV) if on NIV during hospitalization. |
| Change in Patient's Oxygen Partial Pressure | 4 days | PaO2 measured in arterial puncture at baseline and 4 days. |
| Change in Patient's Carbondioxide Partial Pressure | 4 days | PaCO2 measured in arterial puncture at baseline and 4 days. |
| Change of pH in Blood | 4 days | pH measured in arterial puncture at baseline and 4 days. |
| Time for no Oxygen Supplement (or Regular Oxygen Supplement LTOT) | 14 days | Time for no oxygen supplement (or regular oxygen supplement LTOT) if on oxygen during admission. |
| Number of Readmissions (All Causes) | 30 days | — |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control This arm will receive standard care and placebo in 15 days.
Placebo oral tablet: Placebo Azithromycin
Placebo oral tablet: Placebo Hydroxychloroquine | 56 |
| Intervention This arm will receive standard care and azithromycin and hydroxychloroquine in 15 days.
Azithromycin: Azithromycin
Hydroxychloroquine: Hydroxychloroquine | 61 |
| Total | 117 |
Baseline characteristics
| Characteristic | Control | Intervention | Total |
|---|---|---|---|
| Age, Continuous | 63 years | 68 years | 65 years |
| Race/Ethnicity, Customized Race/ethnicity African | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/ethnicity Asian | 6 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Race/ethnicity Caucasian | 45 Participants | 53 Participants | 98 Participants |
| Race/Ethnicity, Customized Race/ethnicity Unknown/other | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Denmark | 56 Participants | 61 Participants | 117 Participants |
| Sex: Female, Male Female | 27 Participants | 25 Participants | 52 Participants |
| Sex: Female, Male Male | 29 Participants | 36 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 56 | 1 / 61 |
| other Total, other adverse events | 25 / 56 | 31 / 61 |
| serious Total, serious adverse events | 2 / 56 | 0 / 61 |
Outcome results
Primary
Number of Days Alive and Discharged From Hospital Within 14 Days
Time frame: 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Number of Days Alive and Discharged From Hospital Within 14 Days | 9 days |
| Intervention | Number of Days Alive and Discharged From Hospital Within 14 Days | 9 days |
Secondary
Categorization of Hospitalization Status
The patient will be categorized into one of the following 8 categories depending on status of their hospitalization: 1. Dead (yes/no) 2. Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) 3. Hospitalized and receiving Non-invasive ventilation or high-flow oxygen device (yes/no) 4. Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) 5. Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) 6. Hospitalized for observation (yes/no) 7. Discharged from hospital with restriction of activity level (yes/no) 8. Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be yes.
Time frame: 14 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Categorization of Hospitalization Status | Dead | 2 Participants |
| Control | Categorization of Hospitalization Status | Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) | 1 Participants |
| Control | Categorization of Hospitalization Status | Hospitalized and receiving Non-invasive ventilation or high-flow oxygen device | 0 Participants |
| Control | Categorization of Hospitalization Status | Hospitalized and given oxygen supplements different from (2) and (3) | 2 Participants |
| Control | Categorization of Hospitalization Status | Hospitalized and without oxygen, but receiving other treatment (both related to COVID-19 or other) | 2 Participants |
| Control | Categorization of Hospitalization Status | Hospitalized for observation | 0 Participants |
| Control | Categorization of Hospitalization Status | Discharged from hospital with restriction of activity level | 27 Participants |
| Control | Categorization of Hospitalization Status | Discharged from hospital without any restrictions of activity level | 22 Participants |
| Intervention | Categorization of Hospitalization Status | Discharged from hospital without any restrictions of activity level | 26 Participants |
| Intervention | Categorization of Hospitalization Status | Dead | 1 Participants |
| Intervention | Categorization of Hospitalization Status | Hospitalized and without oxygen, but receiving other treatment (both related to COVID-19 or other) | 1 Participants |
| Intervention | Categorization of Hospitalization Status | Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) | 3 Participants |
| Intervention | Categorization of Hospitalization Status | Discharged from hospital with restriction of activity level | 26 Participants |
| Intervention | Categorization of Hospitalization Status | Hospitalized and receiving Non-invasive ventilation or high-flow oxygen device | 1 Participants |
| Intervention | Categorization of Hospitalization Status | Hospitalized for observation | 1 Participants |
| Intervention | Categorization of Hospitalization Status | Hospitalized and given oxygen supplements different from (2) and (3) | 2 Participants |
Secondary
Change in Patient's Carbondioxide Partial Pressure
PaCO2 measured in arterial puncture at baseline and 4 days.
Time frame: 4 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Change in Patient's Carbondioxide Partial Pressure | 1.4 mmHg |
| Intervention | Change in Patient's Carbondioxide Partial Pressure | -3.0 mmHg |
Secondary
Change in Patient's Oxygen Partial Pressure
PaO2 measured in arterial puncture at baseline and 4 days.
Time frame: 4 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Change in Patient's Oxygen Partial Pressure | -0.2 mmHg |
| Intervention | Change in Patient's Oxygen Partial Pressure | -3.0 mmHg |
Secondary
Change of pH in Blood
pH measured in arterial puncture at baseline and 4 days.
Time frame: 4 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Change of pH in Blood | 0.0 pH |
| Intervention | Change of pH in Blood | 0.0 pH |
Secondary
Days Alive and Discharged From Hospital
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Days Alive and Discharged From Hospital | 26 days |
| Intervention | Days Alive and Discharged From Hospital | 26 days |
Secondary
Length of Hospitalization
Time frame: 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Length of Hospitalization | 4 days |
| Intervention | Length of Hospitalization | 4 days |
Secondary
Length of Stay in ICU
Length of stay in intensive care unit.
Time frame: 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Length of Stay in ICU | 11 days |
| Intervention | Length of Stay in ICU | 14 days |
Secondary
Mortality
Time frame: 90 days
Secondary
Mortality
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Mortality | 2 Participants |
| Intervention | Mortality | 1 Participants |
Secondary
Mortality
Time frame: 365 days
Secondary
Number of Days Using Non-invasive Ventilation (NIV)
Number of days using non-invasive ventilation (NIV) if on NIV during hospitalization.
Time frame: 14 days
Population: The Overall Number of Participants Analyzed represents the number of participants with available data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control | Number of Days Using Non-invasive Ventilation (NIV) | 9.0 days |
| Intervention | Number of Days Using Non-invasive Ventilation (NIV) | 6.7 days |
Secondary
Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization | 1 Participants |
| Intervention | Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization | 3 Participants |
Secondary
Number of Readmissions (All Causes)
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Number of Readmissions (All Causes) | 6 Participants |
| Intervention | Number of Readmissions (All Causes) | 9 Participants |
Secondary
Time for no Oxygen Supplement (or Regular Oxygen Supplement LTOT)
Time for no oxygen supplement (or regular oxygen supplement LTOT) if on oxygen during admission.
Time frame: 14 days
Population: The Overall Number of Participants Analyzed represents the number of participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Time for no Oxygen Supplement (or Regular Oxygen Supplement LTOT) | 72 hours |
| Intervention | Time for no Oxygen Supplement (or Regular Oxygen Supplement LTOT) | 72 hours |