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

SARS-CoV Infection Clinical Trial

— CloroCOVID19  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04323527
• Other study ID #: CAAE: 30152620.1.0000.0005
• Status: Completed
• Phase: Phase 2
• Start date: March 23, 2020
• Est. completion date: June 7, 2020

Study information

• Verified date: August 2021
• Source: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: June 7, 2020
• Est. primary completion date: May 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Male and female participants aged over 18 years old

2. Hospitalized

3. presenting:

• respiratory rate higher than 24 breathing incursions per minute AND/OR

• heart rate higher than 125 beats per minute (in the absence of fever) AND/OR

• peripheral oxygen saturation lower than 90% in ambient air AND/OR

• shock (defined as mean arterial pressure less than 65 mmHg, requiring vasopressor or oliguria or lowering level of consciousness)

Exclusion Criteria:

• None.

Related Conditions & MeSH terms

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

Intervention

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).

Locations

Country	Name	City	State
Brazil	Hospital e Pronto Socorro Delphina Rinaldi Abdel Aziz	Manaus	Amazonas

Sponsors (10)

Lead Sponsor	Collaborator
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado	Felipe Gomes Naveca, Fernando Fonseca de Almeida e Val, Gisely Cardoso de Melo, Jorge Souza Mendonça, Ludmila Abrahão Hajjar, Marcus Vinícius Guimarães de Lacerda, Maria Paula Gomes Mourão, Mayla Gabriela Silva Borba, Wuelton Marcelo Monteiro

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality rate reduction of 50% by day 28	proportion of deaths at day 28 between groups compared	28 days after randomization
Secondary	Absolute mortality on days 7 and 14	number of deaths at days 7 and 14 between groups compared	7 and 14 days after first dose
Secondary	Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28	clinical status	14 and 28 days after first dose
Secondary	Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization	clinical status	during and after intervention, up to 28 days
Secondary	Duration of supplemental oxygen (if applicable)	supplemental oxygen	during and after intervention, up to 28 days
Secondary	Duration of mechanical ventilation (if applicable)	mechanical ventilation	during and after intervention, up to 28 days
Secondary	Absolute duration of hospital stay in days	hospitalization	during and after intervention, up to 28 days
Secondary	Prevalence of grade 3 and 4 adverse events	adverse events grade 3 and 4	during and after intervention, up to 28 days
Secondary	Prevalence of serious adverse events	adverse events	during and after intervention, up to 28 days
Secondary	Change in serum creatinine level	increase or decrease in serum creatinine compared to baseline	during and after intervention, up to 28 days
Secondary	Change in serum troponin I level	increase or decrease in serum troponin I compared to baseline	during and after intervention, up to 28 days
Secondary	Change in serum aspartate aminotransferase level	increase or decrease in serum aspartate aminotransferase compared to baseline	during and after intervention, up to 28 days
Secondary	Change in serum CK-MB level	increase or decrease in serum aspartate aminotransferase compared to baseline	during and after intervention, up to 28 days
Secondary	Change in detectable viral load in respiratory tract swabs	virus clearance from respiratory tract secretion	during and after intervention, up to 28 days
Secondary	Viral concentration in blood samples	viremia in blood detected through RT-PCR	during and after intervention, up to 28 days
Secondary	Absolute number of causes leading to participant death (if applicable)	death	during and after intervention, up to 28 days