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

Phase 2

Terminated

Conditions: Infection Viral
Virus Diseases
Corona Virus Infection

Interventions: Drug: Placebo oral tablet
Drug: Azithromycin
Drug: Hydroxychloroquine

Registration Number: NCT04322396

Lead Sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 117

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo oral tablet	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
Intervention	Azithromycin	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
Intervention	Hydroxychloroquine	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

Primary Outcome Measures

Name	Time	Method
Number of Days Alive and Discharged From Hospital Within 14 Days	14 days

Secondary Outcome Measures

Name	Time	Method
Mortality	365 days
Number of Readmissions (All Causes)	30 days
Days Alive and Discharged From Hospital	30 days
Change of pH in Blood	4 days	pH measured in arterial puncture at baseline and 4 days.
Length of Hospitalization	14 days
Change in Patient's Carbondioxide Partial Pressure	4 days	PaCO2 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 Participants on Non-invasive Ventilation (NIV) During Hospitalization	14 days
Change in Patient's Oxygen Partial Pressure	4 days	PaO2 measured in arterial puncture at baseline and 4 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".
Length of Stay in ICU	14 days	Length of stay in intensive care unit.
Number of Days Using Non-invasive Ventilation (NIV)	14 days	Number of days using non-invasive ventilation (NIV) if on NIV during hospitalization.

Trial Locations

Locations (8): Aalborg Sygehus
🇩🇰
Aalborg, Denmark
Herlev-Gentofte Hospital
🇩🇰
Copenhagen, Denmark
Odense Universitetshospital
🇩🇰
Odense, Denmark
Slagelse Sygehus
🇩🇰
Slagelse, Denmark
Bispebjerg Hospital
🇩🇰
Copenhagen, Denmark
Hvidovre Hospital
🇩🇰
Copenhagen, Denmark
Nordsjællands Hospital
🇩🇰
Hillerød, Denmark
Roskilde Sygehus
🇩🇰
Roskilde, Denmark