Study Critical of Hydroxychloroquine Withdrawn by Medical Journal

By Pat Anson, PNN Editor

One of the world’s most respected medical journals has issued a rare retraction, essentially disowning a controversial study published last month that claimed the use of hydroxychloroquine and chloroquine for treating COVID-19 had no benefit for hospitalized coronavirus patients.

The Lancet issued the retraction after receiving a letter from the study’s authors saying they were unable to complete an independent audit of the data underpinning their analysis. As a result, the authors concluded they “can no longer vouch for the veracity of the primary data sources.”

The study looked at data from nearly 15,000 patients with COVID-19 who received the antimalarial drugs hydroxychloroquine or chloroquine. They were compared to a control group of over 81,000 patients who did not take the drugs. The study included patients being treated at 671 hospitals in North America, Europe, Asia, Africa, South America and Australia.

The study concluded that chloroquine and hydroxychloroquine significantly increased the risk of death for COVID-19 patients, particularly when taken with an antibiotic.

However, soon after publication, critics began questioning the legitimacy of data used in the study, pointing to inconsistencies such as five Australian hospitals reporting more coronavirus deaths than had been found on the entire continent.

In a letter to The Lancet, study authors Mandeep Mehra, Frank Ruschitzka, and Amit Patel said they could not get full access to the data and could not conduct an independent peer-review of their own research:

“After publication of our Lancet Article, several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process.

We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologise to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

The Lancet’s retraction is likely to lead to more claims and conspiracy theories that the coronavirus has been “politicized” by mainstream medicine and left-leaning media to embarrass President Trump.

In recent months, the president and conservative media have touted hydroxychloquine as a possible "game changer" in the treatment of COVID-19. Trump took the drug as a preventative treatment last month after two White House staff members tested positive for coronavirus. A statement from the president’s doctor yesterday indicated he suffered no ill effects.

“I’m not going to get hurt by it. It’s been around for 40 years,” Trump said last month. “For malaria, for lupus, for other things. I take it. Front-line workers take it. A lot of doctors take it."

Hydroxychloroquine is only approved for the treatment of autoimmune diseases such as lupus and rheumatoid arthritis. The FDA has warned against using hydroxychloroquine as a treatment for COVID-19 outside of a hospital or clinical study because of “serious and potentially life-threatening heart rhythm problems.”

The FDA's Adverse Events Reporting System lists over 10,000 reported cases involving hydroxychloroquine in the past decade, many of them serious or resulting in hospitalizations. Nearly 600 people have died since 2010, including 48 deaths so far this year.

A study published yesterday in The New England Journal of Medicine, found that hydroxychloroquine was no better than a placebo in preventing COVID-19 infections.

Prescriptions for Hydroxychloroquine Surge, But Drop for Hydrocodone

By Pat Anson, PNN Editor

Prescriptions for the antimalarial drugs hydroxychloroquine and chloroquine surged dramatically over the last few months, likely due to their off-label use for treating COVID-19, according to a new analysis published in JAMA. The study also found a significant decline in prescriptions for the opioid painkiller Vicodin and other hydrocodone/acetaminophen combinations.  

Researchers at Brigham and Women's Hospital studied prescription drug data from over 58,000 chain, independent and mail-order pharmacies in the U.S. from February 16 to April 25, and compared them to prescriptions over the same period in 2019.

Prescriptions for hydroxychloroquine and chloroquine spiked in mid-March – rising over 2,000 percent in one week -- soon after President Trump began touting the drugs as a possible treatment for the coronavirus. Brigham researchers estimate there were close to half a million additional prescriptions filled for hydroxychloroquine/chloroquine in 2020 compared to the year before.

SOURCE: JAMA

Hydroxychloroquine is only approved by the Food and Drug Administration to treat autoimmune diseases such as lupus and rheumatoid arthritis. Increased demand for the drug and government stockpiling soon led to spot shortages of hydroxychloroquine.

"There have been indications that hydroxychloroquine (HCQ) prescribing had increased and shortages had been reported, but this study puts a spotlight on the extent to which excess hydroxychloroquine/chloroquine prescriptions were filled nationally," said corresponding author Haider Warraich, MD, an associate physician in the Division of Cardiovascular Medicine at the Brigham.

"This analysis doesn't include patients who were prescribed HCQ in a hospital setting -- this means that patients could have been taking the drugs at home, without supervision or monitoring for side effects."

Last month President Trump took hydroxychloroquine for about two weeks with a doctor’s permission, even though the FDA warned that hydroxychloroquine should not be used as a treatment for COVID-19 outside of a hospital or clinical study because it could aggravate heart problems. The drug has been linked to at least 48 deaths in the U.S. so far this year, according to an FDA database.

On Sunday, the White House announced the U.S. supplied Brazil with 2 million doses of hydroxychloroquine. Brazil reported a record 33,274 new cases of the coronavirus over the weekend. Its death toll now ranks only below the United States, Britain and Italy.

Other Drugs Impacted by Pandemic

Brigham researchers say prescriptions for hydrocodone/acetaminophen fell by nearly 22 percent over the study period. There were also notable declines in prescriptions for the antibiotics amoxicillin and azithromycin, the blood pressure drug lisinopril, and the nerve drug gabapentin. Researchers said there are a variety of reasons why the drugs are being prescribed less often.

“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” researchers said. “Steep declines for amoxicillin and azithromycin appeared out of proportion to expected seasonal declines and could represent fewer outpatient prescriptions for upper respiratory tract infection symptoms.”

The pandemic appears to be taking a toll on the nation’s mental health. In the early stages of the outbreak, pharmacy benefit manager Express Scripts reported a surge in prescriptions for anti-anxiety medications such as Xanax and Valium, as well as antidepressants and anti-insomnia drugs.

A recent survey by the Kaiser Family Foundation found that nearly half of Americans said that they or a family member had cancelled or postponed medical care because of the pandemic. About one in every ten said the person’s medical condition worsened as a result of the delayed care.

Study Debunks Use of Hydroxychloroquine for COVID-19

By Pat Anson, PNN Editor

A large international study on the use of hydroxychloroquine and chloroquine for treating COVID-19 has found the antimalarial drugs offer no benefit for hospitalized coronavirus patients and appear to significantly raise the risk of death, particularly when taken with antibiotics.

The study, published in the peer-reviewed journal The Lancet, looked at data from nearly 15,000 patients with COVID-19 who received hydroxychloroquine or chloroquine, with or without the use of antibiotics. They were compared to a control group of over 81,000 patients who did not take the drugs. The study included patients being treated at 671 hospitals in North America, Europe, Asia, Africa, South America and Australia.

(Update: On June 4, The Lancet retracted this study after the authors said were unable to complete an independent audit of their research and concluded they “can no longer vouch for the veracity of the primary data sources.”)

“We found no evidence of benefit of hydroxychloroquine or chloroquine when used either alone or with a macrolide (antibiotic),” researchers said. “Our study included a large number of patients across multiple geographic regions and provides the most robust real-world evidence to date on the usefulness of these treatment regimens. Although observational studies cannot fully account for unmeasured confounding factors, our findings suggest not only an absence of therapeutic benefit but also potential harm.”

The study found that 9.3% of patients in the control group died in the hospital. Of those treated with chloroquine or hydroxychloroquine alone, 16.4% died. The outcomes were even worse for patients who used chloroquine with an antibiotic (22.2%) or hydroxychloroquine with an antibiotic (23.8%).

Researchers also found that serious cardiac arrhythmias, which cause the lower chamber of the heart to beat rapidly and irregularly, were more common in the groups that took hydroxychloroquine or chloroquine.

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19. Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death,” said lead author Mandeep Mehra, MD, Executive Director of the Brigham and Women’s Hospital Center for Advanced Heart Disease.

“Randomised clinical trials are essential to confirm any harms or benefits associated with these agents. In the meantime, we suggest these drugs should not be used as treatments for COVID-19 outside of clinical trials.”

President Trump disclosed this week that he has been taking hydroxychloroquine as a preventative treatment for COVID-19, even though there is only anecdotal evidence the drug may work against the virus. The president said he was prescribed the drug by his physician after two White House staff members were diagnosed with the virus. Trump said he would only take hydroxychloroquine for about two weeks.

The Food and Drug Administration has said hydroxychloroquine or chloroquine should not be used as frontline treatments for COVID-19 outside of hospitals and clinical trials.

The FDA has only approved chloroquine to treat malaria and hydroxychloquine as a treatment for lupus and rheumatoid arthritis. Both drugs have good safety profiles for those conditions.

Chloroquine and hydroxychloquine have been shown to have antiviral effects in laboratory tests, which has sparked interest in their use as potential treatments for COVID-19. Some countries have been stockpiling the drugs. In March, the FDA added hydroxychloquine and chloroquine to its list of drug shortages. Chloroquine was recently taken off the list.

“Several countries have advocated use of chloroquine and hydroxychloroquine, either alone or in combination, as potential treatments for COVID-19,” said co-author Frank Ruschitzka, MD, Director of the Heart Center at University Hospital Zurich.

“Justification for repurposing these medicines in this way is based on a small number of anecdotal experiences that suggest they may have beneficial effects for people infected with the SARS-CoV-2 virus. However, previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed. However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”

In addition to their findings on chloroquine and hydroxychloroquine, researchers also noted that obesity, heart disease, diabetes and smoking raise the risk of death for hospitalized COVID-19 patients. Interestingly, patients being treated with statins or ACE inhibitors for high blood pressure had a lower risk of mortality, suggesting that medications that stabilize the cardiovascular system may be beneficial.