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CROWN CORONATION: Chloroquine RepurpOsing to healthWorkers for Novel CORONAvirus mitigaTION (CROWN CORONA)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04333732
Recruitment Status : Not yet recruiting
First Posted : April 3, 2020
Last Update Posted : May 7, 2020
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Michael Avidan, Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE March 31, 2020
First Posted Date  ICMJE April 3, 2020
Last Update Posted Date May 7, 2020
Estimated Study Start Date  ICMJE May 2020
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Symptomatic COVID-19 [ Time Frame: 3 months ]
    To determine the effectiveness (and minimum effective dose schedule) of chloroquine prophylaxis in preventing laboratory-confirmed symptomatic, laboratory test-confirmed COVID-19 (WHO COVID-19 severity scale score >1) in healthcare workers with repeated exposures to SARS-CoV-2.
  • Peak severity of COVID-19 over the study period [ Time Frame: 3 months ]
    i) Uninfected - no clinical or virological evidence of infection (Score = 0) ii) Ambulatory - no limitation of activities (score=1) or with limitation (Score=2) iii) Hospitalized - mild no oxygen (Score=3) or with oxygen (Score=4) iv) Hospitalized severe - Scores 5-7* v) Dead * Score 5 is non-invasive ventilation or high flow oxygen; Score 6 is intubation with mechanical ventilation; Score 7 is intubation with additional organ support (e.g. pressors, renal replacement therapy, extra corporeal membrane oxygenation [ECMO]) These outcome definitions are based on WHO R&D Blueprint consensus definitions for COVID-19.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
  • Symptomatic COVID-19 [ Time Frame: 3 months ]
    Clinical diagnosis of COVID-19 with limitation of activities (WHO Severity Scale 2-8)
  • Peak severity of COVID-19 over the study period [ Time Frame: 3 months ]
    i) Uninfected - no clinical or virological evidence of infection (Score = 0) ii) Ambulatory - no limitation of activities (score=1) or with limitation (Score=2) iii) Hospitalized - mild no oxygen (Score=3) or with oxygen (Score=4) iv) Hospitalized severe - Scores 5-7* v) Dead * Score 5 is non-invasive ventilation or high flow oxygen; Score 6 is intubation with mechanical ventilation; Score 7 is intubation with additional organ support (e.g. pressors, renal replacement therapy, extra corporeal membrane oxygenation [ECMO]) These outcome definitions are based on WHO R&D Blueprint consensus definitions for COVID-19.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CROWN CORONATION: Chloroquine RepurpOsing to healthWorkers for Novel CORONAvirus mitigaTION
Official Title  ICMJE An International, Multi-site, Bayesian Platform Adaptive,Randomised, Double-blind, Placebo-controlled Trial Assessing the Effectiveness of Varied Doses of Oral Chloroquine in Preventing or Reducing the Severity of COVID-19 Disease in Healthcare Workers
Brief Summary Healthcare workers are at the frontline of the fight against COVID-19, and as such they are at high risk for infection and possibly for serious infection, linked to the extent of their exposure. The CROWN CORONATION trial prioritizes the protection of healthcare workers as a strategy to prevent collapse of healthcare services.
Detailed Description

CROWN CORONATION is a large, Bayesian adaptive, pragmatic, participant-level randomized, multi-center, transdisciplinary, international placebo-controlled trial. It has been designed in accordance with CONSORT guidelines. Randomization will be stratified by age (<50 and >50) and site. Participants will be healthcare workers at risk for contracting SARS-CoV-2. Participants will be randomized into one of four arms:

  • Low-dose (300mg chloroquine base weekly);
  • Medium-dose (300mg chloroquine base twice weekly);
  • High-dose (150 mg chloroquine base daily);
  • Placebo.

In all treatment arms, an induction dose of 1200mg chloroquine base (or equivalent number of placebo tablets in the placebo arm) will be taken in 4 divided daily doses (that is 300mg chloroquine base per day for four days) before starting the low, medium, or high dose regimen.

New dosage-based arm(s) might be added or removed. The trial will evaluate which of the intervention arms is most effective at decreasing the incidence of severe COVID-19 disease, without unacceptable side effects or safety events.

Participants will complete weekly (smart phone- based) data logs, and follow- up information will be collected until 2 months after enrollment or death. In addition, where possible, we will use telemedicine approaches to collection information on participants. We will provide adherence support interventions that have worked and been tested for Human Immunodeficiency Virus Pre-Exposure Prophylaxis (HIV PrEP) (e.g. two-way SMS with check in for those that report symptoms or adverse events). On enrollment, the local trial team will create a new electronic case record from (CRF) on the web-based study database and record basic demographic information. Participants will be given a secure login to enable them to complete an initial participant health questionnaire and the daily data logs.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
A international, multi-site, randomized, double-blinded, placebo-controlled clinical effectiveness
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE COVID 19
Intervention  ICMJE
  • Drug: Low-dose chloroquine

    chloroquine base 300mg (equivalent to 500 mg chloroquine phosphate or 400mg chloroquine sulphate) weekly

    In all treatment arms, an induction dose of 1200mg chloroquine base (or equivalent number of placebo tablets) will be taken in 4 divided daily doses (that is 300mg chloroquine base per day for four days) before starting the low, medium, or high dose regimen.

    Other Name: Aralen
  • Drug: Mid-dose chloroquine

    chloroquine base 300mg (equivalent to 500 mg chloroquine phosphate or 400mg chloroquine sulphate) twice weekly

    In all treatment arms, an induction dose of 1200mg chloroquine base (or equivalent number of placebo tablets) will be taken in 4 divided daily doses (that is 300mg chloroquine base per day for four days) before starting the low, medium, or high dose regimen.

    Other Name: Aralen
  • Drug: High-dose chloroquine

    chloroquine base 150mg (equivalent to 250mg chloroquine phosphate or 200mg chloroquine sulphate) daily

    In all treatment arms, an induction dose of 1200mg chloroquine base (or equivalent number of placebo tablets) will be taken in 4 divided daily doses (that is 300mg chloroquine base per day for four days) before starting the low, medium, or high dose regimen.

    Other Name: Aralen
  • Drug: Placebo

    The placebo equivalent of low, medium and high arm. Low- once weekly Medium - twice weekly High - daily

    In all treatment arms, an induction dose of 1200mg chloroquine or base (or equivalent number of placebo tablets) will be taken in 4 divided daily doses (that is 300mg chloroquine base per day for four days) before starting the low, medium, or high dose regimen.

Study Arms  ICMJE
  • Experimental: Low-dose (300mg chloroquine base weekly)
    Chloroquine base 300 mg administered orally as chloroquine once weekly. The decision of whether to offer chloroquine will be based on local availability.
    Intervention: Drug: Low-dose chloroquine
  • Experimental: Medium-dose (300mg chloroquine base twice weekly)
    Chloroquine base 300 mg administered orally as chloroquine twice weekly. The decision of whether to offer chloroquine will be based on local availability.
    Intervention: Drug: Mid-dose chloroquine
  • Experimental: High-dose (150 mg chloroquine base daily)
    Chloroquine base 150 mg administered orally once daily either a chloroquine . The decision of whether to offer chloroquine will be based on local availability.
    Intervention: Drug: High-dose chloroquine
  • Placebo Comparator: Placebo
    Placebo 1 - 1 placebo tablet administered orally once daily, Placebo 2 - two placebo tablets administered orally twice weekly, Placebo 3 - two placebo tablets administered orally once weekly. All Placebo groups will take two placebo tablets daily on day 1, day 2, day 3 and day 4, before continuing to a daily, twice weekly or weekly schedule to complete 3 months of administration.
    Intervention: Drug: Placebo
Publications * Not Provided

*   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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 2, 2020)
55000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  1. Volunteers without clinical evidence of COVID-19 infection aged 18 years and older.
  2. Healthcare workers based in a primary, secondary or tertiary healthcare setting with a high risk of developing COVID-19 due to their potential exposure to patients with SARS-CoV-2 infection.
  3. Must have a mobile phone and access to the internet for data collection purposes.
  4. Participants who are willing and able to provide informed consent via an electronic consent process.

Exclusion criteria

  1. Weight outside range 50 kg - 120 kg (110 lbs - 265 lbs).
  2. Prior enrolment into this or other COVID-19 interventional prevention or treatment trials (observational trials not excluded).
  3. Self-reported or diagnosed current infection with SARS-CoV-2 or previous COVID-19 diagnosis.
  4. Self-reported current acute respiratory infection.
  5. Concurrent and/or recent involvement in other research or use of chloroquine/hydroxychloroquine or any other 4-aminoquinolone or another experimental investigational medicinal product that is likely to interfere with the study medication within three months of study enrolment.
  6. Current use of antimalarial agents (lumefantrine, mefloquine, pyronaridine or amodiaquine) or any other drugs that may cause a dangerous drug interaction as listed in Appendix 3.
  7. Self-reported known allergies to the IMP and excipients of IMP and placebo.
  8. Self-reported presence or history of the following conditions: Retinopathy or retinal disease; Cardiomyopathy (structural or ischemic heart disease); Cardiac arrhythmia; known personal or family history of prolonged QTc; Psoriasis; Porphyria cutanea tarda; Epilepsy; Myasthenia gravis; Myopathy of any cause; Serious hepatic or renal disease; Electrolyte abnormalities; self-reported severe depression or suicidality; currently undergoing treatment for tuberculosis.
  9. Self-reported current use of medication with known serious hepatotoxic effects or known interaction with chloroquine as listed in Appendix 3, including anti-TB treatment
  10. Self-reported use of medications which prolong the QTc interval
  11. Inability or unwillingness to be followed up for the trial period
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: Linda Yun, BS 314-273-2240 lindayun@wustl.edu
Contact: Sherry McKinnon, BS 314-286-1768 smckinnon@wustl.edu
Listed Location Countries  ICMJE Canada,   Ireland,   South Africa,   United Kingdom,   United States,   Zambia
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT04333732
Other Study ID Numbers  ICMJE 202004099
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in the main publication may be shared, after de-identification.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: From 3 months after the last patient last visit onward.
Access Criteria: Investigators whose proposed use of the data has been approved by a review committee identified for this purpose.
Responsible Party Michael Avidan, Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Bill and Melinda Gates Foundation
Investigators  ICMJE
Principal Investigator: Michael S. Avidan, MBBCh Washington Univeristy School of Medicine
Principal Investigator: Ramani Moonesinghe, MD University College, London
Principal Investigator: Helen Rees, MD Wits University
PRS Account Washington University School of Medicine
Verification Date May 2020

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