Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04323527
Recruitment Status : Completed
First Posted : March 26, 2020
Last Update Posted : July 7, 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

Tracking Information
First Submitted Date  ICMJE March 19, 2020
First Posted Date  ICMJE March 26, 2020
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE March 23, 2020
Actual Primary Completion Date May 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
Mortality rate reduction of 50% by day 28 [ Time Frame: 28 days after randomization ]
proportion of deaths at day 28 between groups compared
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2020)
Absolute mortality at day 28 [ Time Frame: 28 days after drug first dose ]
number of deaths at day 28 between groups compared
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2020)
  • 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
  • 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
  • Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization [ Time Frame: during and after intervention, up to 28 days ]
    clinical status
  • Duration of supplemental oxygen (if applicable) [ Time Frame: during and after intervention, up to 28 days ]
    supplemental oxygen
  • Duration of mechanical ventilation (if applicable) [ Time Frame: during and after intervention, up to 28 days ]
    mechanical ventilation
  • Absolute duration of hospital stay in days [ Time Frame: during and after intervention, up to 28 days ]
    hospitalization
  • Prevalence of grade 3 and 4 adverse events [ Time Frame: during and after intervention, up to 28 days ]
    adverse events grade 3 and 4
  • Prevalence of serious adverse events [ Time Frame: during and after intervention, up to 28 days ]
    adverse events
  • Change in serum creatinine level [ Time Frame: during and after intervention, up to 28 days ]
    increase or decrease in serum creatinine compared to baseline
  • 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
  • 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
  • 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
  • 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
  • Viral concentration in blood samples [ Time Frame: during and after intervention, up to 28 days ]
    viremia in blood detected through RT-PCR
  • Absolute number of causes leading to participant death (if applicable) [ Time Frame: during and after intervention, up to 28 days ]
    death
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chloroquine Diphosphate for the Treatment of Severe Acute Respiratory Syndrome Secondary to SARS-CoV2
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • SARS-CoV Infection
  • Severe Acute Respiratory Syndrome (SARS) Pneumonia
Intervention  ICMJE Drug: Chloroquine diphosphate
150mg chloroquine diphosphate tablets.
Other Name: chloroquine
Study Arms  ICMJE
  • Active Comparator: Low Dose Chloroquine Diphosphate (5 days)
    Low dose chloroquine group 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.
    Intervention: Drug: Chloroquine diphosphate
  • Active Comparator: High Dose Chloroquine Diphosphate (10 days)
    High dose chloroquine group 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.
    Intervention: Drug: Chloroquine diphosphate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 2, 2020)
278
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2020)
440
Actual Study Completion Date  ICMJE June 7, 2020
Actual Primary Completion Date May 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04323527
Other Study ID Numbers  ICMJE CAAE: 30152620.1.0000.0005
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: all patient data will be shared after study publication
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: after study publication
Access Criteria: upon request to researchers
Responsible Party Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Study Sponsor  ICMJE Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Collaborators  ICMJE
  • 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
Investigators  ICMJE Not Provided
PRS Account Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP