Azithromycin added to hydroxychloroquine for patients admitted
to intensive care due to coronavirus disease 2019
(COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU

J 2020

Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU

DUSKA, Frantisek, Petr WALDAUF, Milada HALACOVA, Václav ZVONÍČEK, Jakub BALA et. al.

Basic information

Original name

Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU

Authors

DUSKA, Frantisek (203 Czech Republic, guarantor), Petr WALDAUF (203 Czech Republic), Milada HALACOVA (203 Czech Republic), Václav ZVONÍČEK (203 Czech Republic, belonging to the institution), Jakub BALA (203 Czech Republic), Martin BALIK (203 Czech Republic), Jan BENES (203 Czech Republic), Olga KLEMENTOVA (203 Czech Republic), Irena KOZAKOVA (203 Czech Republic), Viktor KUBRICHT (203 Czech Republic), Anna LE ROY (203 Czech Republic), Tomas VYMAZAL (203 Czech Republic), Veronika REHOROVA (203 Czech Republic) and Vladimir CERNY (203 Czech Republic)

Edition

TRIALS, London, BMC, 2020, 1745-6215

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30223 Anaesthesiology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.279

RIV identification code

RIV/00216224:14110/20:00116141

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1186/s13063-020-04566-x

UT WoS

000551908000012

Keywords in English

Novel coronavirus; COVID-19; SARS-CoV-2; Azithromycin; Hydroxychloroquine; Respiratory failure

Abstract

V originále

BackgroundNovel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection.MethodsDesign: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). Participants: Adult (>18years) within 24h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for >= 1week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800mg orally in two doses followed by 400mg daily in two doses and azithromycin 500mg orally in one dose followed by 250mg in one dose for a total of 5days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90.DiscussionAlthough both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival.Trial registrationClinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).

Citovat

DUSKA, Frantisek, Petr WALDAUF, Milada HALACOVA, Václav ZVONÍČEK, Jakub BALA, Martin BALIK, Jan BENES, Olga KLEMENTOVA, Irena KOZAKOVA, Viktor KUBRICHT, Anna LE ROY, Tomas VYMAZAL, Veronika REHOROVA and Vladimir CERNY. Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU. TRIALS. London: BMC, 2020, vol. 21, No 1, p. 1-11. ISSN 1745-6215. Available from: https://dx.doi.org/10.1186/s13063-020-04566-x.

@article{1673237,
   author = {Duska, Frantisek and Waldauf, Petr and Halacova, Milada and Zvoníček, Václav and Bala, Jakub and Balik, Martin and Benes, Jan and Klementova, Olga and Kozakova, Irena and Kubricht, Viktor and Le Roy, Anna and Vymazal, Tomas and Rehorova, Veronika and Cerny, Vladimir},
   article_location = {London},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13063-020-04566-x},
   keywords = {Novel coronavirus; COVID-19; SARS-CoV-2; Azithromycin; Hydroxychloroquine; Respiratory failure},
   language = {eng},
   issn = {1745-6215},
   journal = {TRIALS},
   title = {Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU},
   url = {https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04566-x},
   volume = {21},
   year = {2020}
}

TY  - JOUR
ID  - 1673237
AU  - Duska, Frantisek - Waldauf, Petr - Halacova, Milada - Zvoníček, Václav - Bala, Jakub - Balik, Martin - Benes, Jan - Klementova, Olga - Kozakova, Irena - Kubricht, Viktor - Le Roy, Anna - Vymazal, Tomas - Rehorova, Veronika - Cerny, Vladimir
PY  - 2020
TI  - Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU
JF  - TRIALS
VL  - 21
IS  - 1
SP  - 1-11
EP  - 1-11
PB  - BMC
SN  - 17456215
KW  - Novel coronavirus
KW  - COVID-19
KW  - SARS-CoV-2
KW  - Azithromycin
KW  - Hydroxychloroquine
KW  - Respiratory failure
UR  - https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04566-x
L2  - https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04566-x
N2  - BackgroundNovel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection.MethodsDesign: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). Participants: Adult (>18years) within 24h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for >= 1week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800mg orally in two doses followed by 400mg daily in two doses and azithromycin 500mg orally in one dose followed by 250mg in one dose for a total of 5days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90.DiscussionAlthough both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival.Trial registrationClinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).
ER  -

DUSKA, Frantisek, Petr WALDAUF, Milada HALACOVA, Václav ZVONÍČEK, Jakub BALA, Martin BALIK, Jan BENES, Olga KLEMENTOVA, Irena KOZAKOVA, Viktor KUBRICHT, Anna LE ROY, Tomas VYMAZAL, Veronika REHOROVA and Vladimir CERNY. Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU. \textit{TRIALS}. London: BMC, 2020, vol.~21, No~1, p.~1-11. ISSN~1745-6215. Available from: https://dx.doi.org/10.1186/s13063-020-04566-x.

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