Hydroxychloroquine — touted by President Donald Trump as a ‘game changer’ and a ‘gift from God’ in the fight against Covid-19 — doesn’t treat the disease and may even raise the risk of death, another study has found.
A review of 29 scientific studies showed the controversial anti-malarial drug does not save the lives of infected patients.
And when it’s combined with the antibiotic azithromycin — a combination which has been tested in trials — the risk of death increases by 27 per cent, results showed.
The findings support those of a ‘scandalous’ study in May which warned it raised the risk of death. It was later retracted over concerns the data was not reliable.
And the world’s biggest coronavirus drug trial, led by Oxford University researchers, concluded the drug does not treat hospitalised patients. Experts warned the results were ‘pretty compelling’ and pulled the drug from experiments.
Researchers of the latest study, led by Université Paris Saclay, France, claimed there is ‘no need’ for further trials to see if hydroxychloroquine boosts the survival odds of hospitalised patients.
The bold claims are in stark contrast to those of Oxford researchers, who argued this month that it has been discarded prematurely and still needs rigorous testing to find out if it can protect people from getting infected in the first place.
President Trump has complained the medicine became politically toxic because of his support. Some studies — which scientists say are considerably weaker because they don’t compare it against a placebo — have shown it has a benefit.
The malaria drug hydroxychloroquine doesn’t treat treat Covid-19 and may even cause death, another study has found
President Trump has continuously embraced hydroxychloroquine and even admitted to taking it himself with proof it works, despite contradicts from top public health agencies and officials
Thibault Fiolet and colleagues conducted the meta-analysis of hydroxychloroquine when given to Covid-19 patients, either with or without the addition of azithromycin.
Azithromycin is used to treat a wide range of bacterial infections, but has also been promoted as a potential treatment for Covid-19 due to its alleged antiviral or anti-inflammatory properties.
In lab experiments, the two drugs combined have shown to have antiviral properties against the coronavirus in a petri dish.
The authors found 29 research papers, and all except one of which were conducted on hospitalised patients.
Some 11,932 patients were given hydroxychloroquine, 8,081 both drugs, and 12,930 received neither — the ‘control group’.
Results, published in a medical journal, showed hydroxychloroquine did not reduce the number of deaths, overall.
The risk of death for patients given hydroxychloroquine was 17 per cent lower than those in the control group. But an analysis revealed it was nine per cent higher in the three randomised controlled trials examined.
Randomised controlled trials are considered the highest standard of research, and are therefore the most reliable.
They compared patients randomly given the drug under trial with a control group, removing any potential factors that could skew the results.
WHY IS HYDROXYCHLOROQUINE CONTROVERSIAL?
Hydroxychloroquine – branded as Plaquenil – is a cheap drug that has been used to prevent malaria and treat lupus and rheumatoid arthritis for decades.
It was touted as a wonder drug by Donald Trump despite no evidence it could treat Covid-19.
Hope was sparked early on in the crisis when a French study suggested the drug could have both antiviral and anti-inflammatory effects.
It triggered a flurry of research across the world, the endorsement from Trump and emergency authorization from US regulators.
The RECOVERY trial was the first randomised study to provide concrete evidence about the drug.
Leading doctors have also warned the drug can cause severe side effects, and can even throw off the process that makes the heart beat in time.
One trial in Brazil was stopped short because so many of the enrolled coronavirus patients given the drug developed these arrhythmias (abnormal heartbeats).
According to WebMD, side effects may include:
- Nausea, vomiting, loss of appetite, diarrhea, dizziness, or headache
- Slow heartbeat, symptoms of heart failure (such as shortness of breath, swelling ankles/feet, unusual tiredness, unusual/sudden weight gain)
- Mental/mood changes (such as anxiety, depression, rare thoughts of suicide, hallucinations)
- Hearing changes (such as ringing in the ears, hearing loss), easy bruising/bleeding
- Signs of infection or liver disease
- Muscle weakness, unwanted/uncontrolled movements (including tongue/face twitching), hair loss, hair/skin color changes
- Low blood sugar, severe dizziness, fainting, fast/irregular heartbeat, seizures.
The rest of the trials were observational, meaning doctors recorded the outcomes of patients given specific drugs but can’t be certain it was the drug that caused the effect. For instance, doctors may have also given patients other treatment.
Overall, the changes in mortality rates across the papers were not statistically significant, meaning it cannot be proven that any increase or decrease in deaths were directly down to the drug and not chance.
However, the combination of hydroxychloroquine and azithromycin did show a statistically significant 27 per cent increase in mortality, compared with controls.
The authors wrote: ‘These results confirm the preliminary findings of several observational studies which have shown that the combination of hydroxychloroquine and azithromycin might increase the risk of acute, life-threatening cardiovascular events.’
‘There is already a great number of studies that have evaluated hydroxychloroquine alone or in combination and it seems unlikely at this stage that any efficacy will ever emerge.
‘Our results suggest that there is no need for further studies evaluating these molecules, and the European DisCoveRy and WHO international Solidarity clinical trials have already discontinued treatment arms using hydroxychloroquine.’
The study is published in Clinical Microbiology and Infection, the official journal of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
The findings support those of a study retracted from the medical journal The Lancet on June 4, which warned against using hydroxychloroquine because it increases the risk of death in Covid-19 patients by up to 45 per cent.
And Covid-19 patients taking the drug were up to five times more likely to develop a life-threatening arrhythmia – a known side effect of the medication.
More than 120 prominent scientists raised questions about the data used in the study, which was sourced from a database run by a private company, Surgisphere.
The research, led by Dr Mandeep Mehra of Harvard Medical School, Dr Amit Patel of the University of Utah and Dr Frank Ruschitzka of the University Hospital Zurich, was reviewed.
After mounting doubts over the study’s reliability, the authors retracted their study from the Lancet medical journal, whose editorial standards were also thrown into question.
But the damage had already been done – with the suspension of the Solidarity trial, run by the World Health Organization, Oxford University’s RECOVERY trial and a trial in France.
The latest study suggests their findings were not as questionable as first thought.
The debate about hydroxychloroquine as a coronavirus treatment may have finally been put to bed after a slew of studies have found no benefit – and a risk of potentially deadly heart arrythmias
HYDROXY RAISES RISK OF DEATH, ‘SCANDALOUS’ NOW-RETRACTED STUDY WARNED
The research of nearly 100,000 Covid-19 patients, published in prestigious medical journal The Lancet, cast doubt over the efficacy of hydroxychloroquine for the treatment of Covid-19.
But it was retracted on June 4 after mounting doubts over the study’s reliability.
As well as uncovering hydroxychloroquine had no benefit for coronavirus patients, results showed it raised the risk of death by up to 45 per cent.
And Covid-19 patients taking the drug were up to five times more likely to develop a life-threatening arrhythmia – a known complication.
Experts at Brigham and Women’s Hospital in Boston, Massachusetts, analysed data from 96,032 hospitalised Covid-19 patients spanning six continents.
Around 5,000 of the infected were either given hydroxychloroquine or its derivative chloroquine.
Another 10,000 were given hydroxychloroquine or chloroquine alongside two other promising drugs, antibiotics azithromycin or clarithromycin.
Data from those four groups was then compared against a control sample of 81,000 Covid-19 patients, who were given other medications.
Analysis showed one in 11 patients in the control group died in hospital – at a rate of 9.3 per cent.
In comparison, 18 per cent of patients given hydroxychloroquine succumbed to the illness. The rate was 16 per cent among the chloroquine group.
When the two drugs were used in combination with one of the antibiotics, the death rate rose to almost a quarter of patients (23.8 per cent).
Researchers cautioned that some of the difference in the rates of mortality was due to underlying differences between which patients received the treatment.
But when other factors known to raise the risk of death were included – such as age, race, BMI and co-morbidities – the drugs still increased the risk of dying by between 34 and 45 per cent.
The study added to past research that showed taking hydroxychloroquine could raise the risk of someone developing an abnormal heartbeat.
Scientists in the US and France last month found 90 per cent of critically-ill COVID-19 patients given hydroxychloroquine developed heart arrhythmias.
Massachusetts General Hospital researchers monitored 90 patients in intensive care units, while University of Lyon academics analysed 40 patients.
Both uncovered similar results in JAMA Cardiology, after looking at the QT intervals – the time between the heart’s ventricular muscles contracting and then relaxing.
When this interval becomes too long, the patient has developed a dangerous form of heart arrhythmia, called atrial fibrillation.
British researchers behind the only remaining large global trial testing whether hydroxychloroquine can prevent infection say the drug was prematurely discarded, however.
The COPCOV Trial is a double-blind placebo study which aims to enroll 40,000 healthcare workers to see if hydroxychloroquine acts as to prevent catching the coronavirus.
It is being led by the University of Oxford, the London-based research charity the Wellcome Trust and the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Bangkok.
In a press release distributed on August 7, MORU warned dropping the drug will block science from finding out if the medicine can really stop coronavirus from entering the body, potentially saving thousands of lives.
Sir Jeremy Farrar, director of the Wellcome Trust, said: ‘Despite all the publicity, we still do not know if hydroxychloroquine can prevent Covid-19, but it’s really important that we find out, one way or the other.’
The team warned their work was in jeopardy because hydroxychloroquine has become too politicised.
President Trump has touted hydroxychloroquine as a wonder drug from the beginning of the pandemic with no evidence it could treat Covid-19, which has led to political flare-ups and scandals in the scientific field.
Hope was sparked early on in the crisis when a French study suggested the drug could have both antiviral and anti-inflammatory effects.
It triggered a flurry of research across the world, the endorsement from Trump and emergency authorization from US regulators, the FDA.
But since, research on Covid-19 patients has produced disappointing results.
Oxford University, who pulled the controversial drug from the RECOVERY trial amid concerns of its safety, showed a quarter of NHS patients given hydroxychloroquine died from Covid-19, compared to 23.5 per cent who were not prescribed the drug.
The scientists running the trial, which has recruited more than 1,500 patients from around 170 UK hospitals, said the results were ‘pretty compelling’, adding: ‘This isn’t a treatment that works.’
New York researchers said patients received no benefits whether they took just the drug or paired it with the antibiotic azithromycin.
The team looked at 1,438 COVID-19 patients across 25 hospitals in New York, publishing their findings in the Journal of the American Medical Association in May.
They found patients who received a combination of the drugs were more likely to go into cardiac arrest compared to those who took just one of the medications or neither of them.
Heart arrhythmias are a known and potentially life-threatening side effect of the malaria and lupus drug.
Researchers in the US and France carefully monitored 90 and 40 patients, respectively, for heart arrhythmias.
Each found that more than 90 per cent of coronavirus patients in ICUs showed longer-than-normal delays between heartbeats, a worrisome sign that the drug might be disrupting their cardiac function.
In an accompanying editorial in JAMA Cardiology, Northwestern University cardiologist Dr Robert Bonow warned that once these signs emerge, ‘allowing treatment beyond these limits…in patients with Covid-19 should not be recommended unless there are clear benefits associated with anti-inflammatory or antiviral effects that are yet to be clinically demonstrated.’
Another trial in Brazil was stopped early because so many of the enrolled coronavirus patients given the drug developed irregular heartbeats, a known complication of the drug.
But other studies have suggested hydroxychloroquine has improved the survival and recovery odds for about 90 per cent of patients treated.
The Association of American Physicians and Surgeons (AAPS) presented data on 2,333 patients treated with hydroxychloroquine. Results showed 91.6 per cent of those who got the controversial drug fared better after treatment, it was reported at the end of April.