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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

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.

Condition or disease Intervention/treatment Phase
COVID 19 Drug: Low-dose chloroquine Drug: Mid-dose chloroquine Drug: High-dose chloroquine Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55000 participants
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
Official Title: 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
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

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.
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

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.
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

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.
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.





Primary Outcome Measures :
  1. 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.

  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.




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. 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

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): NCT04333732


Contacts
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Contact: Linda Yun, BS 314-273-2240 lindayun@wustl.edu
Contact: Sherry McKinnon, BS 314-286-1768 smckinnon@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Contact: Linda Yun, BS    314-273-2240    lindayun@wustl.edu   
Contact: Sherry McKinnon    314-286-1768    mckinnos@anest.wustl.edu   
Principal Investigator: Michael S. Avidan, MBBCh, FCASA         
Sub-Investigator: Mary Politi, MD         
Principal Investigator: Eric Dubberke, MD         
Canada, Ontario
Population Health Resarch Institute
Hamilton, Ontario, Canada, L8L 2X2
Contact: Jessica Spence, MD, FRCPC       spencej@phri.ca   
Principal Investigator: Jessica Spence, MD, FRCPC         
University of Toronto
Toronto, Ontario, Canada, M5G 1E2
Contact: David Mazer, MD    (416) 864-5825    David.Mazer@unityhealth.to   
Principal Investigator: David Mazer, MD         
Ireland
St James's Hospital
Dublin, Leinster, Ireland, Dublin 8
Contact: Ellen O'Sullivan, MD, FRCA,FCAI    353876993178    ellenosullivan2000@gmail.com   
South Africa
Universitas Academic Hospital
Bloemfontein, Free State, South Africa, 9301
Contact: Edwin Turton, MBChB, Dip PEC, DA, MMed, FCA    +27 82 804 6839    turtonew@ufs.ac.za   
Principal Investigator: Edwin Turton, MBChB, Dip PEC, DA, MMed, FCA         
Wits RHI, University of the Witwatersrand
Johannesburg, Gauteng, South Africa, 2001
Contact: Sinead Delany-Moretlwe, MBChB, PhD, DTM&H    +27 82 377 6275    sdelany@wrhi.ac.za   
Contact: Michelle Moorhouse, MBChB         
Sub-Investigator: Gloria Maimela, MBBCh MBA         
Sub-Investigator: Saiqa Mullick, MBBCh PhD         
Sub-Investigator: Catherine Martin, MBBCh MSc         
Steve Biko Academic Hospital
Pretoria, Gauteng, South Africa, 0001
Contact: Sophie Mathijs, MBChB, MPharmMed    +27 836506425    sandra.spijkerman@up.ac.za   
Principal Investigator: Sophie Mathijs, MBChB, MPharmMed         
Tygerberg Hospital
Cape Town, Western Cape, South Africa, 7505
Contact: Coenraad Koegelenberg, MBChB, MMED, FCP, MRCP, PhD    +27 833201307    coeniefn@sun.ac.za   
Contact: Sean Chetty, MBChB, FCA, PhD         
Sub-Investigator: Coenraad Koegelenberg, MBChB, MMED, FCP, MRCP, PhD         
Sub-Investigator: Sean Chetty, MBChB, FCA, PhD         
Groote Schuur Hospital
Cape Town, Western Cape, South Africa, 7925
United Kingdom
University College London
London, United Kingdom
Contact: Laurence Lovat, MD, PhD    020 3447 7488    laurence.lovat@nhs.net   
Principal Investigator: Laurence Lovat, MD, PhD         
Sub-Investigator: Hakim-Moulay Dehbi, PhD         
Sub-Investigator: Nick Freemantle, PhD         
Sub-Investigator: Dermot McGuckin, MD         
Sub-Investigator: Gemma Jones, MsC         
Sub-Investigator: Ramani Moonesinghe, MD         
Zambia
Levy Mwanawasa University Teaching Hospital
Lusaka, Zambia, 10101
Contact: Laston Chikoya, BSc, MBChB, MMed, MD    +260977349415    chikoyal@yahoo.com   
Contact: Bright Nsokolo, BScHB, MB ChB, MMED    +260977884895    b_nsokolo@yahoo.com   
Principal Investigator: Izukanji Sikazwe, MBChB, MPH         
Sub-Investigator: Roma Chilengi, MBChB, MSc, ACCRP         
Sub-Investigator: Carolyn Bolton, MBBCh, MSc         
Sub-Investigator: Chikumbutso Chipeta, BScHB, MB ChB         
Sub-Investigator: Bright Nsokolo, BScHB, MB ChB, MMED         
Sub-Investigator: Lloyd Mulenga, BScHB, MBCHB, MScID, MMED         
Centre for Infectious Disease Research in Zambia [CIDRZ]
Lusaka, Zambia, H8R9+9V
Contact: Izukanji Sikazwe         
Principal Investigator: Izukanji Sikazwe         
Sub-Investigator: Roma Chilengi         
Sub-Investigator: Carolyn Bolton         
Sub-Investigator: Chikumbutso Chipeta         
Sponsors and Collaborators
Washington University School of Medicine
Bill and Melinda Gates Foundation
Investigators
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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
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Responsible Party: Michael Avidan, Professor of Anesthesiology and Surgery, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04333732    
Other Study ID Numbers: 202004099
First Posted: April 3, 2020    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Avidan, Washington University School of Medicine:
COVID 19
Health care workers
chloroquine
Additional relevant MeSH terms:
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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
Anthelmintics