Dataset from Efficacy and Safety of Chloroquine Diphosphate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV2: a Phase IIb, Double-blind, Randomized Adaptive Clinical Trial

In December 2019, the Municipal Health Committee of Wuhan, China, identified an outbreak of
viral pneumonia of unknown cause. This new coronavirus was called SARS-CoV-2 and the disease
caused by that virus, COVID-19. Recent numbers show that 222,643 infections have been
diagnosed with 9115 deaths, worldwide. Currently, there are no approved therapeutic agents
available for coronaviruses. In this scenario, the situation of a global public health
emergency and evidence about the potential positive effect of chloroquine (CQ) in most
coronaviruses, including SARS-CoV-1, and recent data on small trials on SARS-CoV-2, the
investigators intend to investigate the efficacy and the safety of CQ diphosphate in the
treatment of hospitalized patients with severe acute respiratory syndrome in the scenario of
SARS-CoV2. Preliminary in vitro studies and uncontrolled trials with low number of patients
of CQ repositioning in the treatment of COVID-19 have been encouraging. The main hypothesis
is that CQ diphosphate will reduce mortality in 50% in those with severe acute respiratory
syndrome infected by the SARS-COV2. Therefore, the main objective is to assess whether the
use of chloroquine diphosphate reduces mortality by 50% in the study population. The primary
outcome is mortality in day 28 of follow-up. According to local contingency plan, developed
by local government for COVID-19 in the State of Amazonas, the Hospital Pronto-Socorro
Delphina Aziz, located in Manaus, is the reference unit for the admission of serious cases of
the new virus. The unit currently has 50 ICU beds, with the possibility of expanding to 335
beds, if needed. The hospital also has trained multiprofessional human resources and adequate
infrastructure. In total, 440 participants (220 per arm) will receive either high dose
chloroquine 600 mg bid regime (4x150 mg tablets, every 12 hours, D1-D10) or low dose
chloroquine 450mg bid regime (3x150mg tablets + 1 placebo tablet every 12 hours on D1,
3x150mg tablets + 1 placebo followed by 4 placebo tablets 12h later from D2 to D5, and 4
placebo tablets every 12 hours, D6-D10). Placebo tablets were used to standardize treatment
duration and blind research team and patients. All drugs administered orally (or via
nasogastric tube in case of orotracheal intubation). Both intervention and placebo drugs will
be produced by Farmanguinhos. Clinical and laboratory data during hospitalization will be
used to assess efficacy and safety outcomes.