No benefit of hydroxychloroquine and azithromycin in people hospitalised with COVID-19
17 April 2020. Related: COVID-19: investigational drugs, COVID-19.
Simon Collins, HIV i-Base
A prospective open label study of 11 people (7 men and 4 women) hospitalised with COVID-19 (10/11 with fever) at a single hospital in Paris, reported no benefits from using the antimalaria drug hydroxychloroquine with the antibiotic azithromycin. [1]
The results are important for challenging an earlier French study (from Gautret et al) that reported CoV-2 clearance in 6/26 people using this combination. It led to widespread speculation as an effective treatment that resulted in pharmacy stock-outs within 24 hours. This has drained resources for genuine need (for example, lupus and rheumatoid arthritis). [2, 3]
The new study was authored by Jean-Michel Molina and colleagues from Saint Louis Hospital, Paris and published ahead of print in the French journal Médecine et Maladies Infectieuses.
Baseline characteristics included mean age of 58 years (range: 20 to 77) and 8/11 had significant comorbidities associated with poor outcomes (obesity: 2; solid cancer: 3; hematological cancer: 2; HIV-infection: 1).
The treatment included hydroxychloroquine (600 mg/d for 10 days) and azithromycin (500 mg day 1 and 250 mg days 2 to 5).
After five days, CoV-2 remained detectable by qualitative PCR in throat swabs in all participants.
One patient died and two were transferred to intensive care units. One participant discontinued treatment after four days due to qT prolongation (from 405 ms to 460 and 470 ms).
The paper by Molina et al references a recent randomised study from China that also reported no benefit from hydroxychloroquine and azithromycin in 30 participants, with similar rates of clearance to a control group. In this study, throat swabs were negative by PCR at day seven in 86% of the active vs 93% of the standard of care control groups, and with no differences in clinical outcomes. [4]
It also references other studies showing no impact in other indications and was published as an alert to counter the high publicity given to this combination.
Reference
- Molina JM et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Médecine et Maladies Infectieuses (2020), doi: 10.1016/j.medmal.2020.03.006.
https://www.sciencedirect.com/science/article/pii/S0399077X20300858 - Gautret P et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents 2020 (ahead of print).
https://www.sciencedirect.com/science/article/pii/S0924857920300996 - Yazdany J. Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know. Ann Intern Med. 2020. DOI: 10.7326/M20-1334.
https://annals.org/aim/fullarticle/2764199/use-hydroxychloroquine-chloroquine-during-covid-19-pandemic-what-every-clinician - Chen J et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Journal of Zhejiang University (Medical Sciences). 2020;49(1). doi:10.3785/j.issn.1008-9292.2020.03.03.
http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2020.03.03