Update on Hydroxychloroquine and Azithromycin

It’s the French team from Marseille again – with more data on hydroxychloroquine and azithromycin.

You may remember them from the first, tiny uncontrolled trial featuring hydroxychloroquine monotherapy, and then combination therapy with hydroxychloroquine and azithromycin, with “untreated patients from another center” as their negative controls. This trial, with its grand total of 36 patients has been touted as a miraculous success – as opposed to a small 30 patient trial in China that was unrevealing.

Now we have 80 patients – but worse, still, it is even without any sort of controlled comparison, let alone a randomized, controlled comparison. Minimal enrollment criteria are noted in the publication, but they do note 6 patients are a carryover from their first study. It appears all patients receiving treatment for at least 3 days and received at least 6 days of follow-up were included in the analysis.

The standard treatment protocol is 200mg hydroxychloroquine three times a day, along with a typical 500mg/250mg azithromycin 5 day course. Those with pneumonia and NEWS scores ≥5 received ceftriaxone, as well.

There’s almost no point in mentioning a “primary outcome”, but effectively a good outcome is alive and discharged. Data were collected on viral culture Ct value (the number of amplification cycles required to obtain a positive result).

Overall, 65 of 80 (81.3%) improved and were discharged. One patient was admitted to the ICU and died on day 7 after initiation of treatment. Others have had waxing and waning clinical course in the hospital. Viral culture results, unsurprisingly, mirrored clinical improvement.

The authors infuriatingly suggest: “We believe other teams should urgently evaluate this cost-effective therapeutic strategy.” It is close to unethical to call for others to investigate these agents when they clearly have the means to do so themselves.

The lack of a control group renders these results uninterpretable. Further, the mention in results of “six days of follow-up” for analysis suggests survivorship bias. For a treatment already in widespread use (and misuse), we remain woefully underinformed regarding its true effectiveness and clinical utility.

“Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study”
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf