NCT04323527: CloroCOVID19

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

Completed Phase 2 Last updated 9 August 2021

What this trial tests

Phase 2 trial testing Chloroquine diphosphate in SARS-CoV Infection in 278 participants. Completed in 7 June 2020.

Timeline

23 March 2020

Primary endpoint
7 May 2020

7 June 2020

Quick facts

Lead sponsor	Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	278
Start date	23 March 2020
Primary completion	7 May 2020
Estimated completion	7 June 2020
Sites	1 location across Brazil

Drugs / interventions tested

• Chloroquine diphosphate — full drug profile →

Conditions studied

• SARS-CoV Infection — all drugs for SARS-CoV Infection →
• Severe Acute Respiratory Syndrome (SARS) Pneumonia — all drugs for Severe Acute Respiratory Syndrome (SARS) Pneumonia →

Sponsor

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Who can join

18 and older, any sex, with SARS-CoV Infection or Severe Acute Respiratory Syndrome (SARS) Pneumonia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunology of COVID-19: Current State of the Science.
   Vabret N, Britton GJ, Gruber C, Hegde S, et al · · 2020 · cited 1248× · PMID 32505227 · DOI 10.1016/j.immuni.2020.05.002
2. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.
   Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, et al · · 2020 · cited 696× · PMID 32330277 · DOI 10.1001/jamanetworkopen.2020.8857
3. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts.
   Wang J, Jiang M, Chen X, Montaner LJ. · · 2020 · cited 551× · PMID 32534467 · DOI 10.1002/jlb.3covr0520-272r
4. COVID-19: Transmission, prevention, and potential therapeutic opportunities.
   Lotfi M, Hamblin MR, Rezaei N. · · 2020 · cited 447× · PMID 32474009 · DOI 10.1016/j.cca.2020.05.044
5. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.
   Axfors C, Schmitt AM, Janiaud P, Van't Hooft J, et al · · 2021 · cited 217× · PMID 33859192 · DOI 10.1038/s41467-021-22446-z
6. COVID-19 and Cancer: a Comprehensive Review.
   Gosain R, Abdou Y, Singh A, Rana N, et al · · 2020 · cited 187× · PMID 32385672 · DOI 10.1007/s11912-020-00934-7
7. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
   Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
8. Inflamm-aging: Why older men are the most susceptible to SARS-CoV-2 complicated outcomes.
   Bonafè M, Prattichizzo F, Giuliani A, Storci G, et al · · 2020 · cited 145× · PMID 32389499 · DOI 10.1016/j.cytogfr.2020.04.005