JOURNAL ARTICLE

RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel
Lancet 2020 May 22
32450107

BACKGROUND: Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.

METHODS: We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).

FINDINGS: 96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223-1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368-1·531), chloroquine (16·4%; 1·365, 1·218-1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273-1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935-2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106-5·983), chloroquine (4·3%; 3·561, 2·760-4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344-4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.

INTERPRETATION: We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.

FUNDING: William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.

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John John

The journal admitted certain drawbacks in peer review, leading to withdrawal of the article. Is there any explanation from the authors. Interested to listen to them.

12

Ohoud Salem

Sirag. Can you elaborate more why you think its not accurate

3

Chen Bouvance

Trump:FAKE NEWS!!!
What? This evidence based on the investigation?
Fake investigation !!!




Aye ........Hope this pandemic end as soon as possible

2

David Esteves

Ridículo

1

Mansoor Keen

There might be some drawbacks and inaccuracies from this report, but we have no other genuine evidence supporting their use in COVID,to contradict above data.
To mention prolongation of Qt interval predisposing to arrhythmogenic tendency is a known drug interaction between macrolides and quinines.
If you don't have evidence for do-good, no hype of overdoing it from media pressure.

0

ADEGBENGA ADEMOLU

The standard of peer review need to be upgraded at all times.
Especially in sensitive times and issue like Covid-19 pandemic which have claimed the lives of millions of people, ethical standard cannot be compromised.

0

sirag elsabea

This study it seems funny for me and I am wondering how to find a way to be published in a reputable international magazine !

0

ADEGBENGA ADEMOLU

1. Their geographical distribution of the study cohort over six continents is majorly skewed. With
Australia accounting for only 0.6%,
South America 3.7%
Africa account for only 4.6%,
Asia 7.9%
Europe 17.3%
North America 65.9%
COMMENT
i.Data more applicable to Northern American and probably Europe than other parts of the world.
ii.Pharmacogenetics of drugs was not factored in in this write up, if not they will not attempt to generalize worldwide a data finding that have 3 continents representatives put together in the minority that is Australia (0.6%),South America (3.7%) and Africa with (4.6%).The three continents totalling less than 10% of the cohort studied.

2. The distribution of their cohort study participants into four therapeutic intervention groups is also skewed
Comments
Distribution of participants into the four therapeutic intervention groups by ethnicity was not declared, this is a big flaw in the paper.
For instance,it was reported that 6221 patients received hydroxychloroquine with macrolide,the question is what is the ethnicity of the 6221 patients,were all ethnic group well represented in each of the four groups? The article did not answer that.

3.The article does not explain why subjects treated with antivirals
like lopinavir with ritonavir,
ribavirin and oseltamivir
whether as monotherapy or as combination therapy were not evaluated as a group for outcomes in terms of morbidity and mortality.
COMMENT
This is a pointer to bias in this publication.

4.Details about their control was not detailed enough especially in terms of Nationality, demography,and comorbidity.


-1

José R Luciano S

Estamos frente a una infecciosa aguda enfermedad emergente cuyas contagiosidad y letalidad expusieron las debilidades de los "sistemas" sanitarios donde los había. En la mayoría de los países no existe nada que pudiera denominarse SISTEMA. De existir un sistema funcional, con la tecnología disponible, los ajustes conductuales sociales y económicos el COVID19 no hubiera sobrevivido al invierno boreal.
De hecho, los problemas mas serios siguen relacionados con el rechazo de gran parte de la población a las medidas de distanciamiento social, protección facial e higiene de manos. Con estas previsiones se hubiera controlado la expansión viral, aún sin una terapéutica específica.
Como muestra del desapego a la autorregulación están la persistencia de las infecciones por HIV, lues y otras ETS. También laa pandemias de enfermedades crónicas no transmisibles como la obesidad, diabetes mellitus tipo II y un largo y vergonzoso etc.

-2

Elizabeth Pinkhasov

This study was published in Lancet, but all critics needn’t worry; the Israelis already developed the medicine and vaccine, so, keep your fingers crossed and stay safe.

-5

Ronald Peach

It you spent more time on Medicins and less time attacking president trump you would have a scientific outcome

-7

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