Small Chloroquine Study Halted Over Risk of Fatal Heart Complications – The New York Times

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A research trial of coronavirus patients in Brazil ended after patients taking a higher dose of chloroquine, one of the drugs President Trump has promoted, developed irregular heart rates.

Packets of Nivaquine tablets containing chloroquine, and Plaquenil tablets containing hydroxychloroquine. Both drugs have been promoted by President Trump as a coronavirus treatment.Credit…Gerard Julien/Agence France-Presse — Getty Images

A small study in Brazil was halted early for safety reasons after coronavirus patients taking a higher dose of chloroquine developed irregular heart rates that increased their risk of a potentially fatal heart arrhythmia.

Chloroquine is closely related to the more widely used drug hydroxychloroquine. President Trump has enthusiastically promoted them as a potential treatment for the novel coronavirus despite little evidence that they work, and despite concerns from some of his top health officials. Last month, the Food and Drug Administration granted emergency approval to allow hospitals to use chloroquine and hydroxychloroquine from the national stockpile if clinical trials were not feasible. Companies that manufacture both drugs are ramping up production.

The Brazilian study involved 81 hospitalized patients in the city of Manaus and was sponsored by the Brazilian state of Amazonas. It was posted on Saturday at medRxiv, an online server for medical articles, before undergoing peer review by other researchers. Because Brazil’s national guidelines recommend the use of chloroquine in coronavirus patients, the researchers said including a placebo in their trial — considered the best way to evaluate a drug — was an “impossibility.”

Despite its limitations, infectious disease doctors and drug safety experts said the study provided further evidence that chloroquine and hydroxychloroquine, which are both used to treat malaria, can pose significant harm to some patients, specifically the risk of a fatal heart arrhythmia. Patients in the trial were also given the antibiotic azithromycin, which carries the same heart risk. Hospitals in the United States are also using azithromycin to treat coronavirus patients, often in combination with hydroxychloroquine.

“To me, this study conveys one useful piece of information, which is that chloroquine causes a dose-dependent increase in an abnormality in the ECG that could predispose people to sudden cardiac death,” said Dr. David Juurlink, an internist and the head of the division of clinical pharmacology at the University of Toronto, referring to an electrocardiogram, which reads the heart’s electrical activity.

Roughly half the study participants were given a dose of 450 milligrams of chloroquine twice daily for five days, while the rest were prescribed a higher dose of 600 milligrams for 10 days. Within three days, researchers started noticing heart arrhythmias in patients taking the higher dose. By the sixth day of treatment, 11 patients had died, leading to an immediate end to the high-dose segment of the trial.

The researchers said the study did not have enough patients in the lower-dose portion of the trial to conclude if chloroquine was effective in patients with severe disease. More studies evaluating the drug earlier in the course of the disease are “urgently needed,” the researchers said.

Several clinical trials for chloroquine and hydroxychloroquine are testing low doses for shorter periods of time in coronavirus patients. But the Health Commission of Guangdong Province in China had initially recommended those sick with the virus be treated with 500 milligrams of chloroquine twice daily for 10 days.

One of the authors of the Brazilian study, Dr. Marcus Lacerda, said in an email on Sunday that his study found that “the high dosage that the Chinese were using is very toxic and kills more patients.”

“That is the reason this arm of the study was halted early,” he said, adding that the manuscript was being reviewed by the journal Lancet Global Health.

Dr. Bushra Mina, the section chief of pulmonary medicine at Lenox Hill Hospital in Manhattan, said the study would most likely not change his hospital’s practice of giving a five-day course of hydroxychloroquine and azithromycin to hospitalized patients who were not severely ill. Dr. Mina said patients are monitored daily for heart abnormalities and the drugs are stopped if any are found.

He said the study showed “if you’re going to use it because you have no alternative, then use it cautiously,” he said.

    • When will this end?

      This is a difficult question, because a lot depends on how well the virus is contained. A better question might be: “How will we know when to reopen the country?” In an American Enterprise Institute report, Scott Gottlieb, Caitlin Rivers, Mark B. McClellan, Lauren Silvis and Crystal Watson staked out four goal posts for recovery: Hospitals in the state must be able to safely treat all patients requiring hospitalization, without resorting to crisis standards of care; the state needs to be able to at least test everyone who has symptoms; the state is able to conduct monitoring of confirmed cases and contacts; and there must be a sustained reduction in cases for at least 14 days.

    • What should I do if I feel sick?

      If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others.

    • Should I wear a mask?

      The C.D.C. has recommended that all Americans wear cloth masks if they go out in public. This is a shift in federal guidance reflecting new concerns that the coronavirus is being spread by infected people who have no symptoms. Until now, the C.D.C., like the W.H.O., has advised that ordinary people don’t need to wear masks unless they are sick and coughing. Part of the reason was to preserve medical-grade masks for health care workers who desperately need them at a time when they are in continuously short supply. Masks don’t replace hand washing and social distancing.

    • How does coronavirus spread?

      It seems to spread very easily from person to person, especially in homes, hospitals and other confined spaces. The pathogen can be carried on tiny respiratory droplets that fall as they are coughed or sneezed out. It may also be transmitted when we touch a contaminated surface and then touch our face.

    • Is there a vaccine yet?

      No. Clinical trials are underway in the United States, China and Europe. But American officials and pharmaceutical executives have said that a vaccine remains at least 12 to 18 months away.

    • What makes this outbreak so different?

      Unlike the flu, there is no known treatment or vaccine, and little is known about this particular virus so far. It seems to be more lethal than the flu, but the numbers are still uncertain. And it hits the elderly and those with underlying conditions — not just those with respiratory diseases — particularly hard.

    • What if somebody in my family gets sick?

      If the family member doesn’t need hospitalization and can be cared for at home, you should help him or her with basic needs and monitor the symptoms, while also keeping as much distance as possible, according to guidelines issued by the C.D.C. If there’s space, the sick family member should stay in a separate room and use a separate bathroom. If masks are available, both the sick person and the caregiver should wear them when the caregiver enters the room. Make sure not to share any dishes or other household items and to regularly clean surfaces like counters, doorknobs, toilets and tables. Don’t forget to wash your hands frequently.

    • Should I stock up on groceries?

      Plan two weeks of meals if possible. But people should not hoard food or supplies. Despite the empty shelves, the supply chain remains strong. And remember to wipe the handle of the grocery cart with a disinfecting wipe and wash your hands as soon as you get home.

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      That’s not a good idea. Even if you’re retired, having a balanced portfolio of stocks and bonds so that your money keeps up with inflation, or even grows, makes sense. But retirees may want to think about having enough cash set aside for a year’s worth of living expenses and big payments needed over the next five years.