What is Hydroxychloroquine (Plaquenil)?
Hydroxychloroquine (also known as hydroxychloroquine sulfate), approved for use in 1955 by the FDA, is an arthritis medicine that also can be used to treat and prevent malaria. It is also widely used to treat people with autoimmune disorders such as Rheumatoid Arthritis and Systemic Lupus Erythematous. It is available in the United States by prescription only. It is sold under the brand name Plaquenil and it is also sold as a generic medicine. Hydroxychloroquine can be prescribed to adults and children of all ages. It can also be safely taken by pregnant women and nursing mothers.
Is hydroxychloroquine safe? What are the potential side effects?
Hydroxychloroquine is a relatively well-tolerated medicine, according to the U.S. Centers for Disease Control and Prevention. The most common adverse reactions reported are stomach pain, nausea, vomiting, and headache. These side effects can often be lessened by taking hydroxychloroquine with food. Hydroxychloroquine may also cause itching in some people.
Bear in mind that any vitamin, herbal product and medication can be toxic at extremely high levels. For instance, over the counter Tylenol® is known to cause liver failure at toxic levels, when not taken as directed. Similarly, hydroxychloroquine taken at toxic levels – well beyond the FDA-approved levels used in the WHIP COVID-19 study – have been reported to cause EKG abnormalities. Study volunteers who report a history of heart issues are also not enrolled in the study.
There has also been confusion between the use of hydroxychloroquine as a preventative medication versus a treatment for hospitalized, critically ill patients with COVID-19. The WHIP COVID-19 study looks at the medicine as a potential preventative in normal, otherwise healthy, healthcare workers, first responders, and other essential workers. The doses are the same as those used safely for decades for malaria, lupus and other auto-immune diseases. The use of hydroxychloroquine as a treatment in seriously ill, hospitalized patients is a complete different set of circumstances.
How long is it safe to use hydroxychloroquine?
There is no limit on the use of hydroxychloroquine for the prevention of malaria or other autoimmune infection. When hydroxychloroquine is used at higher doses for many years, a rare eye condition called retinopathy has occurred. People who take hydroxychloroquine for more than five years should get regular eye exams.
Is hydroxychloroquine the same medication as chloroquine (Aralen ®)?
No. Hydroxychloroquine, first made in 1946, is a more soluble and less toxic metabolite of chloroquine; it causes less side effects that chloroquine. These are two different drugs and their chemical names are not interchangeable.
I am already taking hydroxychloroquine for other reasons; can I still enroll in the study?
YES. We are actively enrolling persons currently taking hydroxychloroquine for other medical conditions. These persons will be a cohort group in the study and will do all the same study visits, blood samples, and questionnaires as the other study participants, however, will not be randomized and given medication. These persons will continue taking their already-prescribed dose of hydroxychloroquine.
I have completed the eligibility screening form online and I have not heard anything back.
If you are study eligible at the time you filled out the online screening form, you will be immediately invited to read the study consent form and watch the study consent video online. Once you sign the consent form and submit other required study documents, you will be invited to self-schedule a baseline enrollment visit over the phone with study staff. The link will arrive in an email, so please watch you “spam” and “junk” mail folders.
If you have not heard from us in a week, please call the WHIP Study team at 313-574-2651 or email us at: email@example.com
Will I get paid to be a part of the study?
There is no compensation for being a part of the WHIP COVID-19 Study and there is no charge to participate in the trial.
How long will my participation be in the WHIP COVID-19 Study?
What if I am pregnant and/or breast feeding?
Hydroxychloroquine has been deemed safe by the FDA to prescribe to pregnant and/or breast-feeding women; therefore all pregnant and breast-feeding women are eligible to enroll in the trial.
What dose of Hydroxychloroquine are you using?
When will I get my blood test results?
Blood samples will be taken at your enrollment visit, week 4 visit, and final study visit. Test results will not be available for several months as we are waiting for FDA approved antibody assays that have high sensitivity and specificity to give the most accurate and reliable results to patients. When they become available, all participants that have given a blood sample, will be notified of their results.
Does your study involve treating persons with active COVID-19 infection?
Our study is focused on Prevention and Prophylaxis only, at this time. We only enroll those persons that are otherwise healthy and are not experiencing any signs or symptoms of active COVID-19 infection. We are not currently treating anyone with active COVID-19 infection through the WHIP COVID-19 study.
Does the hydroxychloroquine supply being given for the study affect the medication supply of people already taking hydroxychloroquine for other medical conditions?
No. The Hydroxychloroquine being used for this study was donated from the Strategic National Stockpile and does not impact the availability of hydroxychloroquine to commercial pharmacies.
Where is the science behind Hydroxychloroquine for COVID-19?
Hydroxychloroquine has been found to be effective in stopping SARS-CoV-2 infection in a laboratory setting (not in humans). To date, the largest study in France demonstrated of 1061 COVID-19 patients treated with hydroxychloroquine and azithromycin (for at least 3 days) had lower rates of death (0.8%) compared to patients who did not receive this regimen 13.5%. Preliminary data collected in the register of Italian Rheumatological society reports of 65,000 patients (Lupus and Rheumatoid Arthritis) on long-term hydroxychloroquine, only 20 patients have tested positive for the SARS-CoV-2 virus, and to date there have been no deaths. Additionally, a South Korean study examining post-exposure prophylaxis using hydroxychloroquine found that of the 205 individuals (184 patients and 21 healthcare workers) given hydroxychloroquine after a known COVID-19 exposure and established, negative PCR test at baseline; after 14 days of quarantine, all follow up PCR tests were negative with no serious adverse events having been reported.
What about the reports of hydroxychloroquine causing EKG QT prolongation and cardiac issues?
COVID-19 has been associated with development of heart failure, and myocarditis, a condition known as inflammation of the heart. Myocarditis is known to cause EKG abnormalities, including a fatal cardiac rhythm, known as torsades de points(8). The risk for this effect is increased in patients who are critically ill in the intensive care unit (ICU) setting on life-support (ventilator), requiring use of many IV medications that can add to the risk of EKG QT prolongation abnormalities. WHIP COVID-19 is using hydroxychloroquine for prevention in otherwise healthy participants. If you already know you have EKG QT prolongation not related to taking hydroxychloroquine, you should tell the study staff and not enroll in the study.
Can you explain some of the hydroxychloroquine studies that have been highlighted in the media?
The biggest confusion in study information for hydroxychloroquine is who is being treated and at what point. The WHIP COVID-19 is a preventative study; most of the studies cited in the news are treatment studies of patients already exposed or infected. Reporters also mistakenly interchange “hydroxychloroquine” and “chloroquine,” a stronger and therefore different version of the medicine. Listed below are short summaries of studies most noted in the media. The most common denominator is that all studies that entailed doses identical to WHIP COVID-19 reported no serious side effects.
Updated June 9, 2020
Lancet – On June 4, the British Medical Society’s publication “The Lancet” retracted a study that suggested that sick, hospitalized patients treated with hydroxychloroquine had higher mortality and increased potential for abnormal heart rhythms. The journal found that the data for the study compiled by Surgisphere was unreliable at best and could not be produced for independent review and validation. The move came after scientists and medical researchers around the world discovered flaws in the study’s data. The same day, a different study based on Surgisphere data was also retracted from the New England Journal of Medicine.
Minnesota – Researchers in Minnesota in early June, reported that hydroxychloroquine did not have a preventative effect on people who had been exposed to COVID-19, in a study conducted by the University of Minnesota. Their study participants confirmed they *had* been exposed (at 6 feet or less without proper PPE, within four days of exposure) and were potentially already carrying the novel coronavirus. The WHIP COVID-19 study provides hydroxychloroquine to participants *before* they are exposed and potentially already positive for COVID-19. Also, Minnesota study participants did not have any in-person visits or evaluation as they enrolled in the study; which may have limited investigators’ ability to fully assess the participants’ medical status at enrollment. However, the study’s medication provided at higher doses than used in WHIP COVID-19 proved safe for all participants, with no abnormal cardiovascular events and only minor side effects of some nausea, headaches, diarrhea and upset stomach experienced by about 40% of participants.
Korea study – Researchers in Korea, in a paper published in the International Journal of Antimicrobial Agents, reported that none of the 211 patients and healthcare workers who took hydroxychloroquine after they had been exposed to COVID-19 became infected with the virus. The researchers did not report the outcomes of an additional 105 patients who were enrolled in the study after they were exposed but did not take the medication, other than to say that 26 patients were admitted to the ICU. Minimal side effects were reported among the group who took hydroxychloroquine, including one person with a rash who continued taking the medication and some minor gastrointestinal issues.
India study – Researchers led by India’s Ministry of Health and Family Welfare and the Indian Council of Medical Research compared 378 healthcare workers with symptoms of COVID-19 who eventually tested positive for the virus against 373 who didn’t over a period of a few days in April and May. When the investigators looked back at what the two groups did differently, those who took six or more doses of hydroxychloroquine experienced a protective effect, with a significant reduction of greater than 80% in testing positive for COVID-19. The investigators also noticed a similar but lesser effect in those who took four to five doses of hydroxychloroquine. They also noted that those who did not use PPE properly were at an increased risk of eventually testing positive. Since this study, the Ministry of Health and Family Welfare has advocated that all healthcare workers in India take hydroxychloroquine prophylactically.
Brazil clinical trial stopped early - This study used chloroquine, and not hydroxychloroquine. Extremely high doses of chloroquine were administered beyond US-approved standard of care. Study participants who were on very high doses of chloroquine, were additionally all given intravenous (IV) Ceftriaxone and Azithromycin antibiotics. This triple combination of medications, if given without any monitoring, is expected to cause cardiac side-effects and renal failure with negative cardiac outcomes. This was a critically ill cohort of patients; 43.2% in the ICU at baseline. This manuscript was not peer-reviewed and was not submitted to a scientific journal; hence these failings were not clarified in the discussion.
Negative VA study - This was not a clinical trial. It was not randomized, nor peer-reviewed for quality. This study was a retrospective chart review of previous use of hydroxychloroquine as a *treatment* (not a preventative) in patients already near the end stages of life with multi-organ failure. The findings of the study were as follows: Hydroxychloroquine was added on top of other medications used in the ICU, on patients who had a less than 10% chance of survival. This study did not include confounding medications used, number of organ failures at time of medication administration, nor timing of medication administration within duration of hospitalization.
Obesity and Hydroxychloroquine - There have been recent media reports that individuals who are overweight or obese should not take hydroxychloroquine. There is no scientific or clinical evidence documented or proven, that obese or overweight persons taking hydroxychloroquine are at greater risk for harm. Obesity is NOT a contraindicated condition for taking hydroxychloroquine and it can be safely prescribed regardless of body weight.
If you have any additional questions that we can answer for you, please call the WHIP COVID-19 Study team at 313-574-2651 or email us at: firstname.lastname@example.org