COVID-19: Experts lose enthusiasm for chloroquine treatment


President Trump’s assumption that he can dictate the course of scientific research based on his gut is taking a beating when it comes to chloroquine and hydroxychloroquine, the anti-malaria drugs he’s been promoting as miracle cures for COVID-19.

The latest clinical studies of the drugs’ effects on the disease caused by the novel coronavirus haven’t been encouraging.

Some trials have been pared back or halted because test subjects showed signs of life-threatening side effects.

Some hospitals and medical centres that had been using the drugs as routine first-line treatments for COVID-19 patients have dropped them, reflecting the lack of evidence that they have a positive effect and growing evidence of harm.

And the few clinical studies that have shown any glimmer of hope have turned out to have serious flaws in methodology.

The scariest aspect of the chloroquine craze is that it has become political and partisan.

Back in March, the Food and Drug Administration granted an emergency use authorisation allowing doctors to prescribe chloroquine and hydroxychloroquine for COVID-19 patients.

A few points about that decision. First, it was unnecessary.

Doctors already had the authority to prescribe the drugs, just as they have the power to prescribe any drug for “off-label” use – that is, a use that isn’t affirmatively approved by the FDA.

Second, it was manifestly a response to political pressure exerted by Trump.

Third, it communicated the wrong message to the public.

As Steve Usdin of the healthcare data site Biocentury aptly observed, the action “will be interpreted as a statement by FDA that the drugs should be used to treat COVID-19.”

The FDA has come to no such conclusion, but innocent people will think it has.

Because large-scale randomised clinical trials haven’t been completed, it remains possible that evidence will emerge validating the use of these drugs in treating the disease.

But at the moment, the promotion of the anti-malarials as a treatment for COVID-19 appears centered among right-wing sources such as Fox News, where the drugs are being assiduously pushed by Dr Mehmet Oz via misinterpretations of published data or sheer credulousness; and Trump.

The promotion relies not merely on questionable data, but also anecdotes from patients who attribute their recovery to the malaria drugs but don’t, in fact, have any idea what saved them.

Put it all together, says David Gorski, the veteran pseudoscience debunker at Wayne State University Medical School, and “the evidence that hydroxychloroquine, chloroquine, or the hydroxychloroquine/azithromycin combination is an effective treatment for COVID-19 is getting weaker with every publication.”

Normally, this wouldn’t be much cause for concern. Medical patients resort to useless nostrums all the time.

If the medicaments are innocuous, there’s little harm except to the patients’ pocketbooks.

Problems arise, however, when they divert patients from more time-tested treatments or have damaging side effects themselves.

The latter is the case with chloroquine and hydroxychloroquine.

As we have reported before, they are by no means benign. They have been found to cause heart problems in some patients that can produce sudden death, even when taken for short periods, and have other bad health effects.

Let’s take a look at what genuine clinicians and researchers have found.

Start with the hospitals that have backed away from the malaria drugs as routine COVID-19 treatments. They include the University of Michigan.

“We haven’t seen any clear evidence of benefit so we are not going to use hydroxychloroquine routinely anymore,” Vineet Chopra, head of hospital medicine at Michigan, said on April 2.

“That is based upon the fact that we have been prescribing hydroxychloroquine for a few weeks, did not see therapeutic benefit, but did see adverse effects.”

His view was echoed by Preeti Malani, chief health officer at the university.

“We have moved away from the antimalarial hydroxychloroquine,” she said on a video posted by the Journal of the American Medical Assn.

She added: “We were seeing toxicity – GI (gastrointestinal) side effects and liver toxicity.”

Some clinical trials have been cut back for similar reasons.

Brazilian researchers ended part of a trial of chloroquine treatment prematurely, when several patients subjected to high doses of the drug began to show heart irregularities.

The researchers validated fears about chloroquine’s tendency to increase the so-called QT interval of heart activity, a condition that could lead to life-threatening tachycardia, or rapid heartbeats.

The higher dose “presented toxicity red flags,” the researchers reported in a paper posted on the research website MedRxiv. The paper hasn’t been peer-reviewed.

The researchers said they were treating a group of 41 patients with the high dose and 40 with a lower dose.

The small sample size didn’t allow the researchers to conclude that there was any benefit to the treatment, but “the trend towards higher fatality associated with the higher dose … resulted in a premature halting of this arm.”

A study that examined medical records of 84 COVID-19 patients treated with hydroxychloriquine and the antibiotic azithromycin at NYU found worrisome prolongation of the QT interval among nearly one-third of the patients, including especially serious increases among nine after as little as two days of treatment.

Four of the patients died, though there was no evidence that cardiac problems contributed to their deaths.

French pharmaceutical regulators detected the same phenomenon and issued a warning about prescribing hydroxychloroquine in COVID-19 patients.

They compiled reports of as many as 43 cardiac cases, including as many as seven involving sudden death associated with cardiac issues, in southern France.

“The risks, in particular cardiovascular, associated with these treatments are very present and potentially increased in COVID-19 patients,” the French pharmaceutical safety agency ANSM reported on Friday.

The agency called the report “an important signal” and advised that the drugs should only be used in hospitals and under close medical supervision.

That’s notable because the most eagerly cited source of pro-chloroquine research – including by Dr Oz and President Trump – is a politically well-connected French doctor, Didier Raoult, whose Marseille-based medical institute has issued three studies to date claiming success in treating the coronavirus disease with a preparation of an antibiotic and hydroxychloroquine.

Raoult’s test methods and data, however, have been widely questioned by experts.

None of Raoult’s studies has included a control group – that is, a group of subjects who are not given his treatment, and thus can show if his treatment actually works.

Raoult’s critics point to what appears to be cherry-picking of data to obscure or eliminate adverse outcomes, including the removal of six of the 26 patients in his initial study because their conditions had deteriorated (one had died) or they had stopped the treatment.

Another team of French scientists ripped that study apart.

When the missing subjects were restored, they found, evidence for the positive effect of the treatment was “only anecdotal.”

They concluded “the evidence is substantially weaker than originally reported.”

Solid conclusions about the efficacy of chloroquine or hydroxychloroquine will have to await large-scale clinical trials, but these may be long in coming.

One highly anticipated trial supervised by David Boulware of the University of Minnesota has run into problems recruiting sufficient subjects.

The trial aims to enlist at least about 1,250 subjects who have tested positive for the coronavirus or been exposed to someone who has tested positive.

Thus far, only about 780 subjects have been recruited. The trial will treat half the subjects with hydroxychloroquine and half with a placebo.

Boulware told me by email that he wasn’t sure why recruitment had gone slower than expected. “Optimistically, it would be because new infections are slowing.

Alternatively, it could also be most of our outreach has been via social media, thus internet savvy folks may be more social distancing _ and less infections.

Also, testing is an ongoing problem and most people don’t have testing.”

Once a full complement is enrolled, he says, the trial should yield evidence about the drug in about two weeks.

Barring that or the emergence of any other large-scale, controlled trial, the evidence for the antimalarial drugs remains thin to the point of nonexistent, while evidence for the dangers mounts.

The greatest hazard, of course, comes from those who promote these drugs as a miracle cure to an audience of desperate and fearful people.

This is on Trump. He has caused immeasurable suffering by his incompetent and reckless response to the coronavirus crisis from the start.

Pushing an unproven and potentially harmful treatment on the public makes things even worse. (tca/dpa/NAN)