Randomized Controlled Trial
Study population and setting
The study included 150 patients with laboratory-confirmed SARS-CoV-2 infection admitted to treatment centers in three Chinese provinces between February 11, and February 29, 2020. Patients were randomly assigned to either standard of care (75 patients) or standard of care plus hydroxychloroquine (75 patients; hydroxychloroquine administered for 2-3 weeks). Treatment assignments were known to the patients and providers. Illness severity at admission was generally mild (15%) or moderate (84%), with few severe cases (1%). The primary outcome was the resolution of detectable viral RNA, with a principal secondary outcome of alleviation of clinical symptoms.
The study was terminated early due to declining infection rates and pharmaceutical futility. Patients still under follow-up were censored.
Summary of Main Findings
Among the 150 participants, the average duration of symptoms prior to admission was 16.6 days. Patients were followed for a median of 21 days in the standard of care group, and 20 days in the hydroxychloroquine group. 73% of participants cleared the virus before 28 days of follow-up. There were no differences by study arm in the probability of resolution of detectable virus or the time to resolution. Further, there was no difference by study arm in the probability of alleviation of clinical symptoms or time to alleviation. Participants receiving hydroxychloroquine were more likely to report adverse events (30% vs. 9%) with diarrhea being the most common (10% of patients receiving hydroxychloroquine). No participants died and only one participant, in the hydroxychloroquine group, progressed to severe disease.
The study protocol and follow-up of participants was thorough.
The study included a relatively small sample size, in particular of severe cases. This makes it impossible to assess the potential role of hydroxychloroquine in treating severe disease. Because patients were enrolled on average more than two weeks after disease onset, there is no ability to assess the impact of hydroxychloroqine early in the course of the infection. Further, patients who did not progress to severe disease within this time-period before admission may be a distinct group that would be less likely to benefit from the drug. Finally, the study arm assignment was not blinded which may have biased the reporting and assessment of clinical outcomes and adverse events.
This is one of the first published randomized clinical trials of hydroxychloroquine for COVID-19.
This review was posted on: 12 June 2020