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

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

This study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.

Study Overview

• Status: Terminated
• Conditions: Virus Diseases; Corona Virus Infection; Infection Viral
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Azithromycin; Drug: Placebo oral tablet; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Aalborg Sygehus
  • Copenhagen, Denmark
    • Bispebjerg Hospital
  • Copenhagen, Denmark
    • Hvidovre Hospital
  • Copenhagen, Denmark
    • Herlev-Gentofte Hospital
  • Hillerød, Denmark
    • Nordsjællands Hospital
  • Odense, Denmark
    • Odense Universitetshospital
  • Roskilde, Denmark
    • Roskilde Sygehus
  • Slagelse, Denmark
    • Slagelse Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; 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; Placebo Azithromycin; Drug: Placebo oral tablet; Placebo Hydroxychloroquine
Active Comparator: Intervention; 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: Hydroxychloroquine; Hydroxychloroquine; Drug: Azithromycin; Azithromycin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		30 days
Mortality		90 days
Mortality		365 days
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
Length of Hospitalization		14 days
Days Alive and Discharged From Hospital		30 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

Collaborators and Investigators

• Sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2020
• Primary Completion (Actual): February 2, 2021
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 28, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Disease Attributes; Coronavirus Infections; Infections; Communicable Diseases; Virus Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: KronLungesyg_COVID_19_protokol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No