DETROIT, MI — A new study from the Henry Ford Health System may provide more legitimacy on the use of hydroxychloroquine to treat COVID-19.
Henry Ford published the peer-reviewed study on July 1, using a large-scale perspective analysis of patients from March 10 to May 2. The study looked over 2,500 hospitalized patients from the Henry Ford’s six hospitals, said Dr. Marcus Zervos, division head of infectious disease for Henry Ford Health System.
He said the health system wanted to investigate hydroxychloroquine because data showed that it had some clinical benefit and that it could reduce the inflammatory response in COVID-19 patients early in the pandemic.
“We thought that it would be important to us, or potentially important to use in our patients, (because) we didn’t have any other options that were proven,” Zervos said.
The study concluded that treatment with hydroxychloroquine significantly reduces the death rate of COVID-19 patients, Zervos said. Of those treated with hydroxychloroquine alone, 13% of them died, compared to the 26.4% who died and were were not treated with the drug. There was an overall 18.1% in-hospital mortality rate and patients were over the age of 18, with a median age of 64.
Many of the fatalities involved people with underlying health diseases, according to an article from Henry Ford Health System. These diseases included chronic kidney and lung disease. Mortality of hospitalized patients ranged between 10% and 30% worldwide.
The study also considered treatment using azithromycin. It found that 20.1% patients treated with both azithromycin and hydroxychloroquine died and 22.4% of those treated only with azithromycin died — compared a death rate of 26.4% for those not treated with either drug, according to the Henry Ford health article.
However, despite the findings of the study, the article also stated people should be cautious in their reaction to the seemingly encouraging results. Randomized, controlled trials would still be required to confirm hydroxychloroquine’s effectiveness in treating COVID-19.
“Currently, the drug should be used only in hospitalized patients with appropriate monitoring, and as part of study protocols, in accordance with all relevant federal regulations,” Dr. Zervos said in the article.
Hydroxychloroquine is a drug primarily used to treat malaria and lupus. The drug recently gained notoriety when President Donald Trump touted its effectiveness in treating COVID-19, despite warnings from the FDA, according to an article from USA Today.
Use of the drug to treat COVID-19 remains controversial. Many Michigan health systems, such as Michigan Medicine, Beaumont Health and St. Joseph Mercy decided to either not use hydroxychloroquine or stopped doing so after trying it, according to an article from the Detroit News.
Zervos said the Henry Ford health study was peer-reviewed, unlike some other studies. While some studies have shown that the drug is not effective, he said studies regarding the drug use different doses.
“These studies that have been negative seem to get more attention,” Zervos said. “But there are plenty of studies that have shown benefits have not received as much attention, not just our study.”
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(CNN)The National Institutes of Health announced Saturday that it has halted a clinical trial evaluating the safety and effectiveness of drug hydroxychloroquine as a treatment for adults hospitalized with Covid-19.
“A data and safety monitoring board met late Friday and determined that while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients with Covid-19,” the NIH said in a statement.
The trial enrolled more than 470 adults patients hospitalized with coronavirus, or in an emergency department with anticipated hospitalization. The study found that those patients who were randomly assigned to receive the hydroxychloroquine treatment didn’t benefit from the drug, compared to those in the placebo group.
“In various studies, the drug had demonstrated antiviral activity, an ability to modify the activity of the immune system, and it has an established safety profile at appropriate doses, leading to the hypothesis that it may have also been useful in the treatment of Covid-19,” the NIH said in its statement.
The US Food and Drug Administration on Monday revoked its Emergency Use Authorization for hydroxychloroquine to treat hospitalized patients with coronavirus, saying it was unlikely to provide any benefit based on the latest scientific research.
Starting in mid-March, Trump became a frequent cheerleader for hydroxychloroquine. He promoted the drug repeatedly, despite pleas from scientists to let studies decide if the treatment was safe and effective.
“HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine,” Trump tweeted on March 21.
Fox News frequently echoed Trump, but both the network and the President quieted down about the drugs once studies started showing they didn’t work and possibly could hurt.
A bottle of hydroxychloroquine tablets. | David J. Phillip, File/AP Photo
The Food and Drug Administration on Monday withdrew emergency use authorizations for two coronavirus treatments that President Donald Trump promoted despite concerns about their safety and effectiveness.
The agency revoked the authorizations for hydroxychloroquine and chloroquine after a request from Gary Disbrow, acting director of the Biomedical Advanced Research and Development Authority.
Critics have accused the agency of caving to political pressurewhen it authorized use of hydroxychloroquine and chloroquine in hospitalized Covid-19 patients in late March despite thin evidence. More recent randomized controlled trials have found the drugs do not benefit coronavirus patients, and doctors have reported that hydroxychloroquine can cause heart problems.
Because hydroxychloroquine is approved for other uses — treating lupus and arthritis — doctors could still use it “off label” to treat coronavirus patients, and clinical trials examining their use against Covid-19 can continue. The FDA noted that the version of chloroquine that had been authorized for emergency use is not approved in the U.S. so all use of that drug, donated by Bayer, will now end.
Rick Bright, the former BARDA director whom Disbrow replaced, has accused health officials of removing him from his role overseeing millions of dollars to develop treatments and vaccines because he raised health concerns about hydroxychloroquine and resisted its widespread use.
Drugmakers donated millions of the pill to the government’s strategic national stockpile after Bright wrote to the FDA requesting for emergency use, a move he now says he was pressured to make.
In April, roughly a month after the FDA authorized emergency use of the drugs, the agency warned against using hydroxychloroquine outside of hospitals and clinical trials because of potentially fatal cardiac side effects. Trump toned down on mentions of the pills during his White House briefings around the same time, but in May told reporters he was taking a course of hydroxychloroquine after a White House aide was diagnosed with the coronavirus.
This month two randomized controlled trials, considered the gold standard for determining whether a drug is effective, concluded that the drug does not prevent coronavirus infection and did not help hospitalized patients.
Another study based on tens of thousands of patient records linked hydroxychloroquine to a higher risk of heart problems, but it was withdrawn after questions arose about the quality of the data it used. Doctors have anecdotally reported that the pills, especially when paired with antibiotic azithromycin, can cause heart problems like arrhythmia.
Though drugmakers have donated millions of pills to federal and state governments, it is not clear how many have even been used. Florida, for instance, is sitting on more than 980,000 unused doses from an April donation after just six hospitals put in requests for the drug.
Senate Democrats grilled FDA officials on the emergency use authorization during a Finance Committee hearing this month. Sen. Tammy Baldwin (D-Wisc.) later wrote to Commissioner Stephen Hahn demanding answers on the decision and reasons why it had not been revoked.
Not all researchers have given up on the drug, however, and recent developments show it is not yet dead as a potential weapon against COVID-19, especially as a preventative in people not yet exposed to the virus.
When the company that supplied the data declined to provide the full data set and other information for review, three of the study’s four authors wrote, “Based on this development, we can no longer vouch for the veracity of the primary data sources.”
A day earlier, the World Health Organization recommended that its researchers continue to study the drugs’ potential use against coronavirus, restarting a paused trial.
And researchers across the U.S. are still testing the drug. The 48 or more trials still underway include at least 17 that are testing whether it could still play a role as a prophylactic preventing COVID-19 infection, even if it may not help treat patients who are already infected with the coronavirus.
On Wednesday, the New England Journal of Medicine published the results of a University of Minnesota trial that showed the drug did not help prevent COVID-19 trial in patients who were already exposed to the virus.
Dr. Bradley Connor, the lead investigator for The New York Center for Travel and Tropical Medicine’s trial, was undeterred by the Minnesota results. “Science is based on multiple studies. This doesn’t change anything.”
Connor’s trial examines whether hydroxychloroquine could be a prophylactic prior to exposure to the virus. “I think this deserves further study given the preliminary data from Europe and the in-vitro data would suggest that we need more information.” Connor says enrollment for his team’s double-blinded, randomized placebo-controlled trial is set to begin over the next two weeks and is focused on pre-exposure for healthcare workers.
With eyes on the drug’s preventative role, teams at Duke University Medical Center, ProHEALTH and UnitedHealth Group, NYU Langone Health in New York and Hackensack Meridian Health Corporation in New Jersey tell NBC News they’re continuing or have concluded their trials regardless of recent findings.
A decades-old drug, hydroxychloroquine is traditionally used to treat autoimmune disorders including lupus and arthritis medicine and is also prescribed to prevent malaria. Early in the COVID-19 pandemic, there was evidence the medication might help treat patients with the coronavirus.
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It’s known to have side effects, including muscle weakness and heart arrhythmia, although experts say it’s generally considered safe for a healthy population as long as it’s not prescribed with other medications that could cause arrhythmias.
The University of Minnesota’s study of the antimalarial did not find serious side effects such as cardiac complications, though participants were more likely to have minor gastrointestinal effects like nausea or diarrhea.
Experts say that data point is critical.
“The main takeaway from this study is that hydroxychloroquine, as we suspected, is generally safe. Although the drug did not show a statistically significant benefit when people took it immediately after exposure, it may still have a benefit for prevention prior to exposure,” says Dr. Adrian Hernandez, principal investigator of the HERO research program coordinated by the Duke Clinical Research Institute. Compared to the Minnesota study, the HERO study will give the drug earlier and for a longer duration — 30 days instead of five days.
“This is a well done, really informative study,” says Dr. Daniel Griffin, chief of infectious disease for UnitedHealth Group and ProHEALTH New York. Griffin is leading a two-pronged trial of hydroxychloroquine’s effectiveness preventatively as well as in patients taking it within the first day or two of illness.
In early April, when Griffin’s team first took up their trial, many people had already begun taking the anti-malarial. “It wasn’t so much that I was impressed by any early data,” he said. “It was more that I realized that this was something that people were using. And it was really important to know whether or not it was safe and effective.”
“The reason I say I don’t think it’s a nail in the coffin is that, fortunately, they didn’t find any serious adverse effects … no one’s actually being killed by hydroxychloroquine and that’s what I think puts a nail in the coffin.”
Dr. Michael Belmont, medical director at NYU Langone Orthopedic Hospital, says he is “not especially encouraged, given the experience with active treatment, given the experience with post-exposure prophylaxis, but I still want to complete my study looking at pre-exposure prophylaxis.”
Belmont is the principal investigator of NYU Langone Health’s ongoing trial of hydroxychloroquine for pre-exposure prophylaxis.
Belmont says he has used the drug on rheumatoid arthritis and lupus patients for 35 years without much short-term toxicity, adding that he still sees a possibility that a lower dosage of the drug may prevail in “reducing either the occurrence of symptomatic infection at all, or at least have a mitigating effect so for those that become symptomatic it’s less likely they’ll require hospitalization, ICU, and intubation.”
Politics meets science
Hydroxychloroquine initially became a lightning rod after Trump repeatedly touted it as a preventative measure against the virus. On Wednesday, the White House released results of the president’s latest physical, including that he had taken a two-week course of the drug as well as zinc and vitamin D following the COVID-19 diagnosis of two West Wing staffers.
Medical teams tell NBC News the politicization of the drug has complicated the trial enrollment processes.
“It’s become quite a challenge I think to enroll people in a lot of these trials and actually ever find out if it is particularly attractive preventative or early treatment,” Griffin said.
In his study’s case, initial enrollment was set at 850 participants, although the team is not enrolling new people at the moment. Instead, it’s monitoring the 50 or so participants already enrolled, most of which are healthcare workers. So far, Griffin says there is no evidence of harm or serious adverse effects caused by the trial.
“What we found in our trials was a combination of people not being interested in enrolling, a number of people withdrawing from the trials because either they were concerned or their physician was concerned — and so we ended up in our trials with very limited enrollment,” Griffin explained.
Belmont says while his trial is still on track for completion this September, his team’s experience recruiting their initial target of 350 healthcare worker participants has been similarly paused.
Over the course of recruitment, initial enthusiasm for hydroxychloroquine in active treatment waned and the overall number of acutely ill COVID-19 patients entering NYU’s medical center and exposing themselves to workers declined. Currently there are about 100 participants enrolled in the trial after some workers opted to provide blood samples for the trial’s observational arm instead of taking the drug.
As a result, said Belmont, “I fear I may have lost the ability” to demonstrate a meaningful effect of hydroxychloroquine on acquiring the infection, “but that’s the reality of doing clinical science.” He still hopes to provide insight into how patients tolerate the drug and address other exploratory goals.
Still, at least five groups previously conducting clinical trials of hydroxychloroquine on healthcare workers told NBC News their teams had failed to be approved by review boards, withdrawn, or suspended their trials due to recent trial results, safety concerns or difficulty in enrolling participants.
Montefiore Medical Center in New York officially withdrew its trial of the drug’s treatment of healthcare workers after it was deferred by its IRB, or review board. The study’s principal investigator, Dr. Priya Nori told NBC News, “We didn’t pursue the study further because we just didn’t feel it was worthwhile.” Nori said that hydroxychloroquine was removed from the center’s treatment protocols weeks ago.
Texas Cardiac Arrhythmia Research Foundation in Austin also withdrew its proposal before receiving approval due to safety concerns. Dr. Adam Singer of Stony Brook University in New York said his team did not move forward with its approved trial because “we cannot get healthcare workers to agree to participate in the study.”
In anticipation of a possible second wave of the virus in the fall, Griffin said his team will continue to engage therapies beyond hydroxychloroquine. “As each week, as each month goes by, my hope is that there are more things that are being developed specifically for COVID-19, with even more exciting potential therapeutics and prophylactic medicines that we may want to focus our resources on.”
Today, three of the authors of the paper, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis”, have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they “can no longer vouch for the veracity of the primary data sources.” The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics (COPE) and International Committee of Medical Journal Editors (ICMJE), institutional reviews of Surgisphere’s research collaborations are urgently needed.
The retraction notice is published today, June 4, 2020. The article will be updated to reflect this retraction shortly.
More than 100 scientists have raised concerns over a influential study of hydroxychloroquine and chloroquine that led the World Health Organisation to suspend clinical trials to determine if the drugs could be an effective treatment for Covid-19.
Published last week in The Lancet, the large-scale study suggested the malaria drugs could be dangerous to people with severe cases of Covid-19, increasing the risk of abnormal heart rhythms and even death.
Now, scientists across the world are asking the research team, led by Harvard professor Dr Mandeep Mehra, to release its data for further analysis and independent academic review.
The Lancet study on hydroxychloroquine is going down in flames. ? ??
Remember the WHO halted hydroxychloroquine trials worldwide over this study, after reviewing the data for a mere 48-72 hours over a weekend.
In an open letter, they’ve asked the journal to provide details about the massive hospital database – consisting of 96,000 Covid-19 patients across six continents – which was the basis for the observational study.
So far the authors have declined to release their underlying data, which scientists worry carries several inconsistencies.
Among them are concerns the average daily doses of hydroxychloroquine, which is cheap and easy to administer, used were higher than the recommended amounts – and that data from Australian patients does not match data from the Australian government.
The French government last week revoked a decree authorising hospitals to prescribe hydroxychloroquine for Covid-19 patients after France’s public health watchdog warned against its use.
The move came days after the WHO said safety concerns had prompted it to suspend use of the drug in a global trial.
US president Donald Trump has endorsed the use of hydroxychloroquine and says he has been taken the medication prophylactically – despite confusion over whether or not it works against the coronavirus.
The scientists expressed concerns over a high-profile study from The Lancet, which surveyed 96,000 hospitalized COVID-19 patients across six continents and concluded that the drug was ineffective in fighting the coronavirus and caused serious heart problems and even death for patients who had the disease.
An open letter from more than 180 scientists around the world raised concerns over what they said was inconsistent data in the report, noting that the average daily doses of hydroxychloroquine were higher than the those recommended by the U.S. Food and Drug Administration (FDA).
They also pointed out that data the magazine said was from Australian patients did not seem to match data from the Australian government, among other things.
Another major concern was that the study’s authors did not release their code or data despite signing a pledge to share information on the coronavirus.
The report “has led many researchers around the world to scrutinize in detail the publication in question. This scrutiny has raised both methodological and data integrity concerns,” the scientists wrote, adding that they were asking the Lancet to make available the peer review process that “led to this manuscript being accepted for publication.”
The report in the Lancet was one of several that linked hydroxychloroquine to cardiac issues, but it was the first to link it with a higher rate of deaths. The study found that hospitalized patients who were given hydroxychloroquine were at least 33 percent more likely to die than patients who did not receive the drug.
Two major clinical trials of hydroxychloroquine were put on hold as a result of the study, and the governments of France, Belgium and Italy banned doctors from using it as a coronavirus treatment.
“Many of us in the scientific community were just very angry at seeing a poorly written and executed study published in The Lancet, given loads of publicity, and then having a hugely negative impact on carefully planned clinical trials around the world,” said James Watson, a Thailand-based statistician with the University of Oxford’s Centre for Tropical Medicine and Global Health who helped draft the letter, in an email to BuzzFeed News.
The Lancet spokeswoman Jessica Kleyn told the outlet that the journal will make available the responses to the study, as well as a statement from the authors.
The World Health Organization is temporarily suspending the use of hydroxychloroquine from its global study into experimental treatments for the coronavirus.
WHO Director-General Tedros Adhanom Ghebreyesus said in a news briefing Monday that a study published last week showed those taking hydroxychloroquine had a greater risk of heart problems and death.
Tedros said a “temporary pause” would be implemented on the drug’s use in the trials until the data are reviewed.
“This concern relates to the use of hydroxychloroquine and chloroquine in COVID-19,” he said, noting that it’s safe to use the drug to treat autoimmune diseases and malaria.
Michael Ryan, WHO’s emergencies chief, said the decision was made out of an “an abundance of caution,” and there have not yet been any safety issues with the use of hydroxychloroquine in the trial.
President Trump has championed the drug as a “game changer” in treating coronavirus patients and announced last week he was taking hydroxychloroquine as a preventative measure. Trump has not tested positive for COVID-19.
The Food and Drug Administration approved an emergency use authorization for chloroquine and hydroxychloroquine, a less toxic derivative of chloroquine, to treat some hospitalized patients, but warned the drugs can cause serious heart problems.
“Hydroxychloroquine and chloroquine have not been shown to be safe and effective for treating or preventing COVID-19,” the FDA said.