Chloroquine Diphosphate for the Treatment of Severe Acute Respiratory Syndrome Secondary to SARS-CoV2

Summary

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.

Conditions

• SARS-CoV Infection
• Severe Acute Respiratory Syndrome (SARS) Pneumonia

Interventions

DRUG

Chloroquine diphosphate

150mg chloroquine diphosphate tablets. Note: Tablets used in the study were Chloroquine Diphosphate (produced by Farmanguinhos/Fiocruz), and the dosing stated in the clinicaltrials.gov refers to chloroquine base (in mg).

Sponsors & Collaborators

• Marcus Vinícius Guimarães de Lacerda

  collaborator UNKNOWN

• Mayla Gabriela Silva Borba

  collaborator UNKNOWN

• Wuelton Marcelo Monteiro

  collaborator UNKNOWN

• Gisely Cardoso de Melo

  collaborator UNKNOWN

• Fernando Fonseca de Almeida e Val

  collaborator UNKNOWN

• Felipe Gomes Naveca

  collaborator UNKNOWN

• Maria Paula Gomes Mourão

  collaborator UNKNOWN

• Ludmila Abrahão Hajjar

  collaborator UNKNOWN

• Jorge Souza Mendonça

  collaborator UNKNOWN

• Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-03-23

Primary Completion

2020-05-07

Completion

2020-06-07

Countries

• Brazil

Study Locations