April 16 2020
Hydroxychloroquine (HCQ) largely faded from the news and for a good reason: no one can explain how it may work.
The group led by Wei Tang at Departments of Pulmonology and Critical Care Medicine at Ruijin Hospital, in Shanghai, China, and colleagues conducted multicenter, open label, randomized clinical trial in 16 treatment centers in China in February.
The group enrolled 150 patients hospitalized with COVID-19. 75 patients were assigned to HCQ plus SOC (Standard of Care) and 75 were assigned to SOC alone (control group).
HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively).
Main outcome measures were:
The primary endpoint was the 28-day negative conversion rate of SARS-CoV-2;
The assessed secondary endpoints were:
Negative seroconversion rate at day 4, 7, 10, 14 or 21;
The improvement rate of clinical symptoms;
Normalization of C-reactive protein, and
Blood lymphocyte count within 28-day.
The intention to treat analysis was performed. Adverse events were documented.
Results:
The overall 28-day negative conversion rate was not different between SOC plus HCQ and SOC group (Kaplan-Meier estimates 85.4% versus 81.3%, P=0.341);
Negative conversion rate at day 4, 7, 10, 14 or 21 was also similar between the two groups;
There was no difference in symptoms at 28 days;
A significant efficacy of HCQ on alleviating symptoms was observed when the confounding effects of anti-viral agents were removed in the post-hoc analysis (Hazard ratio, 8.83, 95%CI, 1.09 to 71.3);
There was a significantly greater reduction of CRP (6.986 in SOC plus HCQ versus 2.723 in SOC, milligram/liter, P=0.045) conferred by the addition of HCQ:
There was faster improvement of lymphopenia, albeit no statistical significance;
Adverse events were found in 8.8% of SOC and 30% of HCQ recipients with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea (10%).
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.
Trial registration ChiCTR200002986