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Chloroquine Diphosphate for the Treatment of Severe Acute Respiratory Syndrome Secondary to SARS-CoV2 (CloroCOVID19)

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ClinicalTrials.gov Identifier: NCT04323527
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : April 15, 2020
Sponsor:
Collaborators:
Marcus Vinícius Guimarães de Lacerda
Mayla Gabriela Silva Borba
Wuelton Marcelo Monteiro
Gisely Cardoso de Melo
Fernando Fonseca de Almeida e Val
Felipe Gomes Naveca
Maria Paula Gomes Mourão
Ludmila Abrahão Hajjar
Jorge Souza Mendonça
Information provided by (Responsible Party):
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Brief 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.

Condition or disease Intervention/treatment Phase
SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia Drug: Chloroquine diphosphate Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 23, 2020
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020


Arm Intervention/treatment
Active Comparator: Low Dose Chloroquine Diphosphate (5 days)
Low dose chloroquine group (n=220) consists of 450 mg bid (3 tablets of 150 mg + 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 . Oral administration or via nasogastric tube in case of orotracheal intubation.
Drug: Chloroquine diphosphate
150mg chloroquine diphosphate tablets.
Other Name: chloroquine

Active Comparator: High Dose Chloroquine Diphosphate (10 days)
High dose chloroquine group (n=220) consists of 600 mg bid (4 tablets of 150 mg, every 12 hours) for 10 days. Oral administration or via nasogastric tube in case of orotracheal intubation.
Drug: Chloroquine diphosphate
150mg chloroquine diphosphate tablets.
Other Name: chloroquine




Primary Outcome Measures :
  1. Mortality rate reduction of 50% by day 28 [ Time Frame: 28 days after randomization ]
    proportion of deaths at day 28 between groups compared


Secondary Outcome Measures :
  1. Absolute mortality on days 7 and 14 [ Time Frame: 7 and 14 days after first dose ]
    number of deaths at days 7 and 14 between groups compared

  2. Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28 [ Time Frame: 14 and 28 days after first dose ]
    clinical status

  3. Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization [ Time Frame: during and after intervention, up to 28 days ]
    clinical status

  4. Duration of supplemental oxygen (if applicable) [ Time Frame: during and after intervention, up to 28 days ]
    supplemental oxygen

  5. Duration of mechanical ventilation (if applicable) [ Time Frame: during and after intervention, up to 28 days ]
    mechanical ventilation

  6. Absolute duration of hospital stay in days [ Time Frame: during and after intervention, up to 28 days ]
    hospitalization

  7. Prevalence of grade 3 and 4 adverse events [ Time Frame: during and after intervention, up to 28 days ]
    adverse events grade 3 and 4

  8. Prevalence of serious adverse events [ Time Frame: during and after intervention, up to 28 days ]
    adverse events

  9. Change in serum creatinine level [ Time Frame: during and after intervention, up to 28 days ]
    increase or decrease in serum creatinine compared to baseline

  10. Change in serum troponin I level [ Time Frame: during and after intervention, up to 28 days ]
    increase or decrease in serum troponin I compared to baseline

  11. Change in serum aspartate aminotransferase level [ Time Frame: during and after intervention, up to 28 days ]
    increase or decrease in serum aspartate aminotransferase compared to baseline

  12. Change in serum CK-MB level [ Time Frame: during and after intervention, up to 28 days ]
    increase or decrease in serum aspartate aminotransferase compared to baseline

  13. Change in detectable viral load in respiratory tract swabs [ Time Frame: during and after intervention, up to 28 days ]
    virus clearance from respiratory tract secretion

  14. Viral concentration in blood samples [ Time Frame: during and after intervention, up to 28 days ]
    viremia in blood detected through RT-PCR

  15. Absolute number of causes leading to participant death (if applicable) [ Time Frame: during and after intervention, up to 28 days ]
    death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04323527


Contacts
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Contact: Marcus Lacerda, PhD +55 92 99114 7633 marcuslacerda.br@gmail.com
Contact: Fernando Val, PhD +55 92 99116 3107 ffaval@gmail.com

Locations
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Brazil
Hospital e Pronto Socorro Delphina Rinaldi Abdel Aziz Recruiting
Manaus, Amazonas, Brazil, 69093-415
Contact: Mayla Borba, MD    +5592981519122      
Sponsors and Collaborators
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Marcus Vinícius Guimarães de Lacerda
Mayla Gabriela Silva Borba
Wuelton Marcelo Monteiro
Gisely Cardoso de Melo
Fernando Fonseca de Almeida e Val
Felipe Gomes Naveca
Maria Paula Gomes Mourão
Ludmila Abrahão Hajjar
Jorge Souza Mendonça

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
ClinicalTrials.gov Identifier: NCT04323527    
Other Study ID Numbers: CAAE: 30152620.1.0000.0005
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: April 15, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: all patient data will be shared after study publication
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: after study publication
Access Criteria: upon request to researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado:
COVID-19
SARS-CoV Infection
Severe Acute Respiratory Syndrome (SARS) Pneumonia
Chloroquine Diphosphate
Clinical trial
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Coronavirus Infections
Pneumonia
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Chloroquine
Chloroquine diphosphate
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents