I have repeatedly argued that, based on in vitro evidence, hydroxychloroquine should be prescribed while we wait for the results of clinical trials. Such results were just published. They are very disappointing.
The link is to an LA Times Article: latimes.com 2020-04-17 malaria-drugs-fails-to-help-coronavirus-patients-in-controlled-studies
The University of Chicago Medicine recruited 125 people with Covid-19 into Gilead’s two Phase 3 clinical trials. Of those people, 113 had severe disease. All the patients have been treated with daily infusions of remdesivir.
“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” said Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital.
“It’s always hard,” she said, because the severe trial doesn’t include a placebo group for comparison. “But certainly when we start [the] drug, we see fever curves falling,” she said. “Fever is now not a requirement for people to go on trial, we do see when patients do come in with high fevers, they do [reduce] quite quickly. We have seen people come off ventilators a day after starting therapy. So, in that realm, overall our patients have done very well.”
She added: “Most of our patients are severe and most of them are leaving at six days, so that tells us duration of therapy doesn’t have to be 10 days. We have very few that went out to 10 days, maybe three,” she said.
back to hydroxychloroquine and the very disappointing results
Quick summary of Tang et al pdf warning “The overall 28-day negative conversion rate was not [statisically significantly argg] different between SOC plus HCQ and SOC group (Kaplan-Meier estimates 85.4% versus 81.3%, P=0.341). ”
Conclusions The administration of HCQ did not result in a higher negative conversion rate but more alleviation of clinical symptoms than SOC alone in patients hospitalized with COVID-19 without receiving antiviral treatment, possibly through anti-inflammatory effects. Adverse events were significantly increased in HCQ recipients but no apparently increase of serious adverse events.
Mahevas et al was not a randomized controlled trial as explained by the title “No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial”
This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21) events, relative risk [RR] 0.91, 95% CI 0.47–1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13–2.89),and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65–2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation.
The comparison doesn’t just fail to reject the null that hydroxychloroquine doesn’t help. the outcomes are very similar with and without. It sure suggests any possible benefits are very small (recall the warning that this wasn’t a randomized trial).