Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine and azithromycin
British Journal of Clinical Pharmacology, doi:10.1111/bcp.14482
To assess clinical outcomes and adverse drug events in patients hospitalised with COVID-19 treated with off-label hydroxychloroquine (HCQ) and azithromycin (Az).
Methods: We performed a retrospective analysis of hospitalised patients who had a positive polymerase chain reaction test for SARS-CoV-2 and received HCQ plus Az or no targeted therapy. The primary end point was clinical improvement on day 7 defined as either hospital discharge or an improvement of 2 points on a 6-category ordinal scale. Secondary outcomes included mortality at day 28, intensive care admission, requirement for mechanical ventilation and incidence of adverse events. Results: Data from a total of 134 patients were evaluated; 82 patients received HCQ/Az and 52 patients received no targeted therapy. Clinical improvement was seen in 26.8% of patients who received HCQ/Az but this was not significant. The rates of intensive care transfer and mechanical ventilation were higher in the treatment group, but these differences were not significant. Mortality at day 28 was significantly higher in the treatment group (P = .03). Hypoglycaemia elevated liver function tests and QT prolongation were monitored in both groups. The risk of QT prolongation was significantly higher in the treatment group. Treatment was stopped early in 6 (7.3%) patients due to adverse events.
Conclusion: Although patients who received HCQ/Az were more severely ill the administration of these repurposed drugs did not result in clinical improvement and was associated with a significant increase in toxicity. This descriptive study highlights the importance of monitoring all repurposed agents for adverse events.
COMPETING INTERESTS There are no competing interests to declare.
DATA AVAILABILITY STATEMENT Data available on request due to privacy/ethical restrictions. F I G U R E 1 Intensive care (ICU) transfer and mortality rates between groups
Atkinson, Ryan, Bennett, The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review, Support Care Cancer
Cansu, Korkmaz, Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA, Rheumatology
Cao, Wang, Wen, A trial of Lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med
Chen, Zhou, Dong, Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet
El-Solia, Al-Otaibi, Ak, Hydroxychloroquine-induced hypoglycaemia in non-diabetic renal patient on peritoneal dialysis, BMJ Case Rep, doi:10.1136/bcr-2017-223639
Fossa, Wisialowski, Duncan, Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized Guinea pig, Am J Trop Med Hyg
Hse, Interim Guidance for the Use of Antiviral Therapy in the Clinical Management of
Magagnoli, Narendran, Pereira, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19, medRxiv
Smith, Dodds, Bentley, Yeo, Rayner, Dosing will be a key success factor in repurposing antivirals for COVID-19, Br J Clin Pharmacol, doi:10.1111/bcp.14314