Proactive Protection With Azithromycin and hydroxyChloroquine in Hospitalized Patients With COVID-19

Study Overview
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Brief Summary
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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
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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.

Official Title
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Proactive Protection With Azithromycin and Hydroxychloroquine in Hospitalized Patients With COVID: A Randomized, Placebo-controlled Double-blinded Trial Evaluating Treatment With Azithromycin and Hydroxychloroquine to Patients With COVID-19

Conditions
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Virus Diseases, Infection Viral, Corona Virus Infection

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Hydroxychloroquine
* Drug: Placebo oral tablet
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>This arm will receive standard care and placebo in 15 days. Azithromycin placebo: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 Hydroxychloroquine placebo: Day 1-15: 200 mg x 2 | Drug: Placebo oral tablet<br>* Placebo Azithromycin<br>Drug: Placebo oral tablet<br>* Placebo Hydroxychloroquine<br>|
| Active Comparator: Intervention<br>This arm will receive standard care and azithromycin and hydroxychloroquine in 15 days. Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 Hydroxychloroquine: Day 1-15: 200 mg x 2 | Drug: Azithromycin<br>* Azithromycin<br>Drug: Hydroxychloroquine<br>* Hydroxychloroquine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days Alive and Discharged From Hospital Within 14 Days |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Categorization of Hospitalization Status | The patient will be categorized into one of the following 8 categories depending on status of their hospitalization: Dead (yes/no) Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) Hospitalized and receiving Non-invasive ventilation or high-flow oxygen device (yes/no) Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) Hospitalized for observation (yes/no) Discharged from hospital with restriction of activity level (yes/no) Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be yes. | 14 days | 
| Length of Stay in ICU | Length of stay in intensive care unit. | 14 days | 
| 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 | 
| Mortality |  | 90 days | 
| Mortality |  | 365 days | 
| Number of Readmissions (All Causes) |  | 30 days | 
| Number of Days Using Non-invasive Ventilation (NIV) | Number of days using non-invasive ventilation (NIV) if on NIV during hospitalization. | 14 days | 
| Change in Patient's Oxygen Partial Pressure | PaO2 measured in arterial puncture at baseline and 4 days. | 4 days | 
| Change in Patient's Carbondioxide Partial Pressure | PaCO2 measured in arterial puncture at baseline and 4 days. | 4 days | 
| Change of pH in Blood | pH measured in arterial puncture at baseline and 4 days. | 4 days | 
| 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. | 14 days |