Methods
We selected as eligible studies parallel RCTs evaluating either hydroxychloroquine (HQ) or chloroquine to treat patients diagnosed with COVID-19, used alone or in any combination, and compared with any other treatment option (including placebo). We selected HQ and chloroquine because these drugs have received widespread support as effective treatments for patients diagnosed with COVID-19 infection. These claims arose following demonstration of in vitro viral activity against SARS-CoV-2, and with potential viral load reduction in a case series report.17, 18 In the United States, the FDA issued an emergency use authorization to allow the use of these drugs in adolescents and adults hospitalized for COVID-19 not participating in clinical trials.19 Moreover, social media and leadership support, lead to widespread shortages of the medication. Traditionally, these immune-suppressants have been used to treat autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease; however, they have also been approved for the treatment of malaria since 1955.20 Familiarity and potential benefit have created a push for expedited clinical trials. We included trials recorded in the clinical trial register of any country and at any recruitment status. Uncontrolled trials and observational studies were excluded.
We downloaded the COVID-19 WHO-ICTRP database (https://www.who.int/ictrp/search/en/) on April 8th, 2020 at 10:30 GMT-6. On the database, we filtered studies according to the intervention (HQ or chloroquine) and the study design (randomized versus non-randomized). All the retrieved registers were considered included and reviewed for data extraction purposes. Patients and investigators were not aware of this study at the time of their submissions.