ACP recommends against chloroquine, hydroxychloroquine for COVID-19
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Current evidence does not support the use of chloroquine or hydroxychloroquine — alone or in combination with azithromycin — to treat or prevent COVID-19 outside of clinical trials, according to practice points published by the ACP in the Annals of Internal Medicine.
“Physicians and other clinicians are managing this novel COVID-19 virus on the frontlines in real time with a paucity of evidence available to inform treatment decisions,” Jacqueline W. Fincher, MD, MACP, president of ACP, told Healio Primary Care. “It is critical to provide frontline physicians with the most relevant up to date understanding of these current treatment options to consider whether they are actually appropriate for patients or too great a risk to use, particularly in the ambulatory setting.”
Previously, chloroquine and hydroxychloroquine were touted by President Donald J. Trump and others as a potential treatment for COVID-19, and preliminary results from some studies have shown that they may be effective.
According to the practice points, the antimalarials provide benefits for certain conditions, including rheumatic conditions, and supply of both agents is limited in the United States.
Additionally, the authors of the practice points noted that numerous harms are associated with chloroquine and hydroxychloroquine, including cardiovascular effects like cardiomyopathy, cardiac failure and ventricular arrhythmias, hypoglycemia, anemia, seizures and ophthalmic macular degeneration.
To provide physicians with guidance on these potential treatments for COVID-19, researchers from the University of Connecticut Health Outcomes, Policy and Evidence Synthesis Group conducted a rapid and living systematic review of 10 studies — three randomized control trials, three cohort studies and four case studies.
The researchers found little evidence on the efficacy and safety of chloroquine and hydroxychloroquine for COVID-19. They reported that the findings are conflicting, and the studies are low quality.
Therefore, the authors of the practice points concluded that chloroquine and hydroxychloroquine alone or combined with azithromycin should not be used to treat or prevent COVID-19 in the general population.
However, they stated that chloroquine and hydroxychloroquine can be used to treat hospitalized patients with COVID-19 in a clinical trial setting, as long as the patient has been fully informed about known harms and uncertain benefits of the treatments.
One such clinical trial includes a phase 2b trial recently launched by the NIH, which is evaluating the safety and efficacy of hydroxychloroquine plus azithromycin.
According to a press release, researchers are enrolling participants who test positive for SARS-CoV-2 and exhibit symptoms like fever, cough and shortness of breath. However, the trial breaks from the ACP practice points, as participants take oral medications at home — not while hospitalized.
The practice points are “living guidance,” and the ACP’s Scientific Medical Policy Committee will evaluate new evidence as it becomes available and update the guidance as needed, according to the press release.
“We need every tool in the toolbox available that could be helpful, especially in the seriously ill hospitalized COVID-19 patients,” Fincher said. “While there was some early push for clinical use of these drugs alone or in combination based on their chemical, clinical and possible synergistic properties, the Practice Points provide critical details about the lack of and/or insufficient current research about the benefits and harms for prevention and treatment of COVID-19.”
“It is really only in the context of a clinical trial using shared and informed decision-making with patients and their families that these medications could be safely used in a monitored hospital environment,” Fincher continued. “This type of close monitoring could certainly help mitigate possible harms of the medications while documenting daily clinical response, to truly know if the medications have an applicable role in treatment of COVID-19 or not.” – by Erin Michael
Disclosures: Healio Primary Care was unable to confirm Fincher’s relevant financial disclosures at the time of publication. Please see study for all other authors’ relevant financial disclosures.
Editor’s note: The story was updated to include comments from Fincher and information about the NIH’s phase 2b trial.
Perspective
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Rajesh T. Gandhi, MD
I am overall quite favorable towards ACP Practice Points. They are sending the right message, which is we don’t have enough evidence to support using hydroxychloroquine or chloroquine with or without azithromycin in routine practice. A month or 2 ago, when COVID-19 really began to come up, there was a lot of uncertainty. Time has gone by, and there is just really no good evidence that these drugs are having a beneficial effect. That’s not to say for certain that they don’t, it’s just that we need definitive studies to find out.
Since March, the availability of clinical trials has greatly expanded. It’s fair to say that we have learned more about the toxicity, but the benefit remains uncertain. A lot of the studies that have been released even over the last month have not supported the use of hydroxychloroquine or chloroquine and have even shown harm. Many of the recent studies, however, have been too small to answer the question or have been observational studies, which means that they can be subject to confounding.
At this point, we need a definitive study. In clinical trials, there is the idea of equipoise — when you’re just not sure if something works or doesn’t work. It’s only ethical to do a trial if you’re not sure of the answer. In COVID-19, we absolutely need to know what works and what doesn’t, so getting an answer is critical, and the only way to get an answer is to do a randomized trial, which is large enough to give a definitive answer. It is ethical and appropriate, and to be honest, incumbent on us to do that. In addition to determining whether hydroxychloroquine works for treatment, we need to know whether it has a role in preventing COVID-19. Until we know the answer, I would not recommend using hydroxychloroquine for treatment or prevention of COVID-19 outside of a clinical trial.
The FDA also provided useful guidance that I suspect influenced the preceded the ACP — the FDA issued a warning to clinicians to only use hydroxychloroquine in hospitalized patients, and then they reiterated the potential harms and commented on the importance of doing clinical trials. Many treatment groups now are converging on the same recommendation, including the Infectious Diseases Society of America, and the ACP. For treating clinicians and the public the message is clear: We need to know whether hydroxychloroquine works for COVID-19 and the way to find out is a definitive clinical trial.
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