Post by Admin on Apr 22, 2020 18:22:31 GMT
A panel of experts convened by the National Institute of Allergy and Infectious Diseases recommends against doctors using a combination of hydroxychloroquine and azithromycin for the treatment of COVID-19 patients because of potential toxicities.
"The combination of hydroxychloroquine and azithromycin was associated with QTc prolongation in patients with COVID-19," the panel said.
QTc prolongation increases the risk of sudden cardiac death.
The recommendation against their combined use would seem to fly in the face of comments made by President Trump suggesting the combination might be helpful. On March 21, for example, the president described them in a tweet as having a "real chance to be one of the biggest game changers in the history of medicine."
He has repeatedly touted the use of the drugs during televised coronavirus task force briefings.
"I think it's not a bad idea to do it, but that's up to the doctors," Trump said March 31 before adding the caveat, "It's going to have to be proven. It's very early."
On April 5, though, without any more evidence of efficacy, he went further:
"What do you have to lose? And a lot of people are saying that when — and are taking it — if you're a doctor, a nurse, a first responder, a medical person going into hospitals, they say taking it before the fact is good. But what do you have to lose? They say, 'Take it.' I'm not looking at it one way or the other, but we want to get out of this. If it does work, it would be a shame if we didn't do it early. But we have some very good signs. So that's hydroxychloroquine and azithromycin."
As for using the use of hydroxychloroquine or chloroquine alone, the panel said there was "insufficient clinical data to recommend either for or against." It reached the same conclusion about the drug remdesivir.
The expert panel, convened by the NIH Institute that Dr. Anthony Fauci directs, produced a set of guidelines for doctors to use in treating COVID-19 patients. The panelists come from a variety of health care disciplines. For the most part, the guidelines are agnostic about the use of experimental medications, pointing out that strong scientific evidence is lacking to make a firm conclusion one way or the other.
But occasionally, there are recommendations explicitly against certain therapies. For example, the panel recommended against using Lopinavir/ritonavir or other HIV protease inhibitors because of negative clinical trial data. It also recommended against using interferon because it seemed to make patients with SARS and MERS worse. Those diseases are caused by a coronavirus related to the one causing COVID-19.
"It's all based on the data," said panel member Dr. Susan Swindells, a professor in the department of internal medicine at the University of Nebraska College of Medine. "We just plowed through everything that was, and apart from supportive care, there wasn't anything that was working terribly well."
Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study
doi: doi.org/10.1101/2020.04.08.20054551
Abstract
Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.
"The combination of hydroxychloroquine and azithromycin was associated with QTc prolongation in patients with COVID-19," the panel said.
QTc prolongation increases the risk of sudden cardiac death.
The recommendation against their combined use would seem to fly in the face of comments made by President Trump suggesting the combination might be helpful. On March 21, for example, the president described them in a tweet as having a "real chance to be one of the biggest game changers in the history of medicine."
He has repeatedly touted the use of the drugs during televised coronavirus task force briefings.
"I think it's not a bad idea to do it, but that's up to the doctors," Trump said March 31 before adding the caveat, "It's going to have to be proven. It's very early."
On April 5, though, without any more evidence of efficacy, he went further:
"What do you have to lose? And a lot of people are saying that when — and are taking it — if you're a doctor, a nurse, a first responder, a medical person going into hospitals, they say taking it before the fact is good. But what do you have to lose? They say, 'Take it.' I'm not looking at it one way or the other, but we want to get out of this. If it does work, it would be a shame if we didn't do it early. But we have some very good signs. So that's hydroxychloroquine and azithromycin."
As for using the use of hydroxychloroquine or chloroquine alone, the panel said there was "insufficient clinical data to recommend either for or against." It reached the same conclusion about the drug remdesivir.
The expert panel, convened by the NIH Institute that Dr. Anthony Fauci directs, produced a set of guidelines for doctors to use in treating COVID-19 patients. The panelists come from a variety of health care disciplines. For the most part, the guidelines are agnostic about the use of experimental medications, pointing out that strong scientific evidence is lacking to make a firm conclusion one way or the other.
But occasionally, there are recommendations explicitly against certain therapies. For example, the panel recommended against using Lopinavir/ritonavir or other HIV protease inhibitors because of negative clinical trial data. It also recommended against using interferon because it seemed to make patients with SARS and MERS worse. Those diseases are caused by a coronavirus related to the one causing COVID-19.
"It's all based on the data," said panel member Dr. Susan Swindells, a professor in the department of internal medicine at the University of Nebraska College of Medine. "We just plowed through everything that was, and apart from supportive care, there wasn't anything that was working terribly well."
Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study
doi: doi.org/10.1101/2020.04.08.20054551
Abstract
Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.