Clinical trial NCT04322396: Proactive Protection With Azithromycin and hydroxyChloroquine in Hospitalized Patients With COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Virus Diseases
Infection Viral
Corona Virus Infection
Lead sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Sponsor class: OTHER
First posted: 2020-03-26
Enrollment: 117
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Days Alive and Discharged From Hospital Within 14 Days
timeFrame: 14 days
Secondary outcomes:
measure: Categorization of Hospitalization Status
timeFrame: 14 days
measure: Length of Stay in ICU
timeFrame: 14 days
measure: Number of Participants on Non-invasive Ventilation (NIV) During Hospitalization
timeFrame: 14 days
measure: Mortality
timeFrame: 30 days
measure: Length of Hospitalization
timeFrame: 14 days
measure: Days Alive and Discharged From Hospital
timeFrame: 30 days
measure: Mortality
timeFrame: 90 days
measure: Mortality
timeFrame: 365 days
measure: Number of Readmissions (All Causes)
timeFrame: 30 days
measure: Number of Days Using Non-invasive Ventilation (NIV)
timeFrame: 14 days
measure: Change in Patient's Oxygen Partial Pressure
timeFrame: 4 days
measure: Change in Patient's Carbondioxide Partial Pressure
timeFrame: 4 days
measure: Change of pH in Blood
timeFrame: 4 days
measure: Time for no Oxygen Supplement (or Regular Oxygen Supplement "LTOT")
timeFrame: 14 days
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Sygehus
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Herlev-Gentofte Hospital
city: Copenhagen
country: Denmark
facility: Hvidovre Hospital
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Roskilde
country: Denmark
facility: Roskilde Sygehus
city: Slagelse
country: Denmark
facility: Slagelse Sygehus
Study officials:
References:
citation: Sivapalan P, Ulrik CS, Lappere TS, Eklof JV, Shaker SB, Bodtger UCS, Browatzki A, Meyer CN, Weinreich UM, Laursen CB, Biering-Sorensen T, Knop FK, Lundgren JD, Jensen JS. Proactive prophylaxis with azithromycin and hydroxychloroquine in hospitalized patients with COVID-19 (ProPAC-COVID): a statistical analysis plan. Trials. 2020 Oct 20;21(1):867. doi: 10.1186/s13063-020-04795-0.
citation: Sivapalan P, Ulrik CS, Bojesen RD, Lapperre TS, Eklof JV, Hakansson KEJ, Browatzki A, Tidemansen C, Wilcke JT, Janner J, Gottlieb V, Meteran H, Porsbjerg C, Madsen BL, Moberg M, Pedersen L, Benfield TL, Lundgren JD, Knop FK, Biering-Sorensen T, Ghanizada M, Sonne TP, Bodtger UCS, Jensen SG, Rasmussen DB, Brondum E, Tupper OD, Sorensen SW, Alstrup G, Laursen CB, Moller UW, Sverrild A, Jensen JS. Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 10;21(1):513. doi: 10.1186/s13063-020-04409-9.