The FDA just issued emergency use authorization for HCQ and CQ to treat the coronavirus. What’s the latest on hydroxychloroquine for COVID-19? New Data!
The rollercoaster ride with hydroxychloroquine (HCQ) continues. There was some initial good news from an in vitro (test tube) Chinese study. Then there was more good news from a pilot study in France. But what followed was bad news from a small controlled study in China. Is there some recent good news on hydroxychloroquine for COVID-19?
We suspect something positive is happening. The FDA is cautious and usually moves slowly. The agency just issued an EUA (Emergency Use Authorization) for chloroquine and hydroxychloroquine. The drugs can now be donated to the Strategic National Stockpile and doctors can prescribe them “as appropriate.”
Most U.S. scientists have been skeptical about chloroquine (CQ) and HCQ. How could these cheap old malaria drugs work against this horrific virus? However, the latest reports on hydroxychloroquine for COVID-19 seem upbeat.
The FDA’s Emergency Use Authorization!
Despite the skepticism about the anti-malaria drugs, the FDA has acted with unusual speed to issue an EUA. We have been tracking the FDA’s decisions for over 40 years. The people at the agency who make drug decisions do so very slowly and deliberately. We have never seen such fast action.
Although there is still very little solid scientific evidence supporting the use of CQ or HCQ for the treatment of the coronavirus, the FDA must have seen something to warrant this action.
Here, in the FDA’s own words, is the crux of the emergency use authorization:
“Based on the totality of scientific evidence available to FDA, it is reasonable to believe that chloroquine phosphate and hydroxychloroquine sulfate may be effective in treating COVID-19, and that, when used under the conditions described in this authorization, the known and potential benefits of chloroquine phosphate and hydroxychloroquine sulfate when used to treat COVID-19 outweigh the known and potential risks of such products.”
We cannot prove this, but we believe that the FDA knows more than it is sharing at this time. We repeat, the agency normally moves very slowly and cautiously!
This is a positive development and it will give physicians access to these drugs from the Strategic National Stockpile. That means many very sick patients will soon have access to these drugs…until supplies run out.
A VERY Quick Review:
We first got interested in two very different potential treatments for the coronavirus when we watched a fascinating presentation by Dr. Roger Seheult for www.MedCram.com. Here is a link to his March 12, 2020 Update 35 video on potential treatments that might help control coronavirus.
In it, he explains the antiviral activity of hydroxychloroquine for COVID-19 in the test tube. Dr. Seheult cites Chinese researchers who published their work in the journal Clinical Infectious Diseases (March 9, 2020).
Next, Dr. Seheult describes the antiviral activity of a dietary supplement called quercetin. This flavonoid is found in a variety of foods including fruits, berries and vegetables (onions, kale, broccoli, tomatoes, etc.). Renowned Canadian scientist Michel Chretien describes why he thinks this compound might be helpful against COVID-19 in this CBC video.
Hydroxychloroquine for COVID-19 – Human Data:
French researchers created a furor with their small pilot study in about 20 patients (International Journal of Antimicrobial Agents, online, March 17, 2020). They reported faster viral clearance with the combination HCQ plus the antibiotic azithromycin.
A great many scientists pushed back. This was not a randomized controlled trial. It was tiny by any standard. No clinical improvement was described. Many researchers doubted that the drug was beneficial and some were highly critical of the lead researcher, Dr. Didier Raoult.
A Chinese study (Journal of ZheJiang University, March 6, 2020) involving 30 patients did involve a control group. There was no clinical difference between the people who received conventional therapy and those who got hydroxychloroquine for COVID-19.
So, an in vitro study with some promise. One small observational trial with some promise and one small controlled trial that was a bust.
That’s where we were as of March 26, 2020. Since then, a little more information about HCQ has become public.
The Latest on Hydroxychloroquine for COVID-19:
Dr. Raoult and his colleagues have just described a new observational trial involving 80 patients (“Hydroxychloroquine-Azithromycin and COVID-19”). Like their previous research, this study was not a randomized double-blind, placebo-controlled trial.
This preliminary study involved 80 coronavirus-positive patients. One 86-year-old patient arrived at the hospital very sick and died. One 74-year-old patient was still in the ICU.
The authors describe the remaining 78 patients:
“For all other patients in this cohort of 80 people, the combination of hydroxychloroquine and azithromycin resulted in a clinical improvement that appeared significant when compared to the natural evolution in patients with a definite outcome, as described in the literature.”
“The favourable evolution of our patients under hydroxychloroquine and azithromycin was associated with a relatively rapid decrease in viral RNA load as assessed by PCR [polymerase chain reaction], which was even more rapid when assessed by culture. These data are important to compare with that of the literature which shows that the viral RNA load can remain high for about three weeks in most patients in the absence of specific treatment with extreme cases lasting for more than a month.”
Dr. Raoult’s team concludes that the combination of hydroxychloroquine and azithromycin is effective in the treatment of COVID-19 and encourage other researchers to “urgently evaluate” this approach to:
“…avoid the spread of the disease and to treat patients before severe irreversible respiratory complications take hold.”
Critics say that this study is no better than the previous pilot trial. They don’t quite call it fake medical news, but they get pretty close. Many say that the patients treated with the drugs would probably have gotten better anyway, so no one can say the drugs helped cure these COVID-19 patients. We remain agnostic.
HCQ and RCTs (Randomized Controlled Trials)
The bottom line is that we will need large randomized, double-blind, placebo-controlled trials carried out at multiple centers around the world before we can say definitively that hydroxychloroquine either speeds healing from or prevents transmission of the novel coronavirus that is sweeping the world. It will take months to complete such trials.
One such study is being carried out by the University of Minnesota on 1,500 volunteers. It was just fast-tracked by the FDA. Watch this short video from NBC News (March 28, 2020). You will also see an additional interview with a NYC doctor who is taking and prescribing hydroxychloroquine for COVID-19.
Hydroxychloroquine for COVID-19 in Clinics:
Doctors have always been allowed to prescribe any drug for any purpose they think is medically justifiable. Every day millions of Americans take off-label drugs. It has been estimated that one out of every five outpatient prescriptions is actually prescribed off-label.
Here are just a few examples of drugs being used off-label:
Bevacizmab (Avastin) for macular degeneration.
Gabapentin (Neurontin) for anxiety, restless legs syndrome, fibromyalgia and pain.
Topiramate (Topamax) for bipolar disorder, nerve pain, depression.
Trazodone (Desyrel) for insomnia.
You can learn more about this issue at this link:
Off-Label Prescribing of Hydroxychloroquine for COVID-19:
According to ProPublica (March 29, 2020):
“The University of Washington, the University of Michigan and other academic medical centers have added hydroxychloroquine to their treatment protocols. ‘Hydroxychloroquine is an inexpensive and generally safe drug for short term use, with few drug-drug interactions,’ the University of Washington protocol says. ‘While it is unknown if it is effective to treat COVID-19, there is a favorable risk:benefit and cost ratio. Multiple trials are ongoing, and this recommendation will be updated when further data is available.’”
New York City has already received thousands of doses of HCQ to be used in clinical trials. Governor Cuomo has purchased additional quantities:
“70,000 doses of Hydroxychloroquine, 10,000 doses of Zithromax [azithromycin] and 750,000 doses of Chloroquine.”
Some doctors are already prescribing HCQ to patients who test positive for the virus and are experiencing serious symptoms. We have heard through a very reliable grapevine that many key physicians around the world would likely take hydroxychloroquine (possibly with azithromycin) if they developed serious symptoms of COVID-19.
New York State will be creating a large, unconventional “observational” trial. Data will be collected on viral load, time on a ventilator, days in the hospital and mortality. It is likely to be one of the largest and fastest studies ever conducted and will dramatically expand upon the French research.
The Governor of Florida, Ron DeSantis, secured hydroxychloroquine from the Israeli generic drug company Teva. It will be used in hospitals in counties such as Orange, Dade and Broward. Severely ill patients will be offered access.
The Power of Observation and Common Sense:
There are healthcare professionals and other scientists who would not believe anything that has not been tested in a randomized controlled trial. Yet for thousands of years people used their common sense and the power of observation to make important discoveries. That is how we initially learned about the benefits of aspirin for treating a fever, easing pain and reducing the risk of heart attacks.
Jeff Colyer is a physician. He was also governor of Kansas between 2018 and 2019. His first opinion piece in the Wall Street Journal (March 22, 2020) was co-authored by Dr. Daniel Hinthorn, Director of Infectious Disease at the University of Kansas Medical Center. You can read the highlights in our article at this link.
They admitted that:
“…we are using hydroxychloroquine in two ways: to treat patients and as prophylaxis to protect health-care workers from infection.”
Dr. Colyer has a new opinion piece in the Wall Street Journal (March 29, 2020).
In it, he describes some data collected by Wuhan doctors:
“During the initial Chinese outbreak, Wuhan doctors observed that patients with lupus—a disease for which HC [hydroxychloroquine] is a common treatment—did not seem to develop Covid-19…The Wuhan doctors hypothesized that this may be due to long-term use of HC.”
Dr. Colyer also notes that 20 COVID-19 patients were treated with HCQ in this Wuhan hospital and showed significant improvement.
We realize that this, like other observational studies, is not good enough to draw any meaningful conclusions about hydroxychloroquine for COVID-19. But some good news is accumulating and our fingers are crossed that it might continue.
The Downsides of HCQ!
You can read all about adverse reactions associated with chloroquine and hydroxychloroquine at the bottom of this article:
Sudden Cardiac Death:
One of the most serious potential complications of both hydroxychloroquine and azithromycin is heart rhythm abnormalities. The French doctors performed electrocardiogram screening on all patients in their most recent study. That is important, because people who have something called long QT syndrome (LQTS) are at risk for dangerous heart arrhythmias if they take either hydroxychloroquine or azithromycin. Combined, the risk would probably be even greater.
When people have a long QT interval, the time between heartbeats is prolonged. The symptoms of LQTS can include dizziness, unsteadiness, lightheadedness and fainting. But many people do not know they even have this abnormal electrocardiogram. There is also a genetic test that can reveal the likelihood of LQTS.
Many medications are inappropriate (contraindicated) for people with long QT syndrome. Chloroquine, hydroxychloroquine and azithromycin are all on that list! Before a hospital administers HCQ or azithromycin, we would hope they would also administer an ECG to rule out LQTS. There are some strategies that may be employed that might reduce the risk of arrhythmias.
The People’s Pharmacy Perspective:
We love randomized clinical trials. Data obtained from such research are considered the gold standard. Of course, that is in normal times. We do not live in normal times. The coronavirus causing COVID-19 has changed everything.
We doubt that the early developers of penicillin relied on RCTs.
They gave their crude antibiotic to 170 patients between 1941 and 1942 (Yale Journal of Biology and Medicine, March, 2017):
“The results demonstrated a remarkable effect of penicillin in combating bacterial infections without any toxic side effects.”
“The first trials of penicillin in the war setting were conducted by Florey in the military hospitals in north Africa in 1942, and showed that penicillin was effective when used on both fresh and infected wounds.”
We suspect that those were “observational” studies. We are hopeful that some of the observational trials now underway will reveal whether the interest in hydroxychloroquine (and azithromycin) is warranted. These drugs could flame out and prove ineffective. Ultimately, RCTs will tell the whole story.
One final word of caution from The People’s Pharmacy. We know people with lupus and rheumatoid arthritis. They are friends and relatives. These people absolutely require hydroxychloroquine. They should receive first priority in getting their prescriptions filled. No one with these serious health conditions should have to go without their medicine because of the possibility their medicine might be helpful against the coronavirus! Pharmaceutical manufacturers better get busy making HCQ in case it turns out to work.