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History of Changes for Study: NCT04333732
CROWN CORONATION: Chloroquine RepurpOsing to healthWorkers for Novel CORONAvirus mitigaTION (CROWN CORONA)
Latest version (submitted October 25, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 2, 2020 None (earliest Version on record)
2 April 12, 2020 Arms and Interventions, Study Design, Study Identification, Contacts/Locations, Eligibility, Study Description, Sponsor/Collaborators and Study Status
3 April 29, 2020 Contacts/Locations, IPDSharing, Arms and Interventions, Study Status, Eligibility, Outcome Measures, Conditions and Study Description
4 May 5, 2020 Arms and Interventions and Study Status
5 August 4, 2020 Contacts/Locations, Arms and Interventions, Study Status, Outcome Measures, Study Design, Study Identification, Study Description, Eligibility, Conditions, Oversight and Sponsor/Collaborators
6 August 10, 2020 Contacts/Locations and Study Status
7 August 20, 2020 Contacts/Locations and Study Status
8 August 21, 2020 Sponsor/Collaborators and Study Status
9 September 3, 2020 Study Status
10 September 7, 2020 Recruitment Status, Study Status and Contacts/Locations
11 November 20, 2020 Contacts/Locations, Study Status and Eligibility
12 January 27, 2021 Contacts/Locations, Study Status, Study Description and Study Identification
13 March 11, 2021 Contacts/Locations and Study Status
14 April 13, 2021 Contacts/Locations and Study Status
15 May 11, 2021 Contacts/Locations and Study Status
16 July 19, 2021 Recruitment Status, Study Status, Contacts/Locations and Study Design
17 October 25, 2021 Outcome Measures and Study Status
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Study NCT04333732
Submitted Date:  April 12, 2020 (v2)

Open or close this module Study Identification
Unique Protocol ID: 202004099
Brief Title: CROWN CORONATION: Chloroquine RepurpOsing to healthWorkers for Novel CORONAvirus mitigaTION (CROWN CORONA)
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
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2020
Overall Status: Not yet recruiting
Study Start: April 2020
Primary Completion: February 2021 [Anticipated]
Study Completion: February 2021 [Anticipated]
First Submitted: March 31, 2020
First Submitted that
Met QC Criteria:
April 2, 2020
First Posted: April 3, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
April 12, 2020
Last Update Posted: April 15, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Washington University School of Medicine
Responsible Party: Principal Investigator
Investigator: Michael Avidan
Official Title: Professor of Anesthesiology and Surgery
Affiliation: Washington University School of Medicine
Collaborators: Bill and Melinda Gates Foundation
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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 study 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 or hydroxychloroquine base (or equivalent number of placebo tablets in the placebo arm) will be taken in 4 divided daily doses (that is 300mg chloroquine or hydroxychloroquine base per day for four days) before starting the low, medium, or high dose regimen.

In certain countries (especially where malaria is not endemic), hydroxychloroquine is more readily available and will be used instead of chloroquine. Based on in vitro studies and reviews of drug toxicity, we consider 150mg of hydroxychloroquine base to be equivalent to 150mg of chloroquine base in terms of efficacy. 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.

Open or close this module Conditions
Conditions: COVID 19
Keywords: COVID 19
Health care workers
hydroxychloroquine
chloroquine
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Prevention
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
A international, multi-site, randomized, double-blinded, placebo-controlled clinical effectiveness
Number of Arms: 4
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 55000 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Low-dose (300mg chloroquine base weekly)
Chloroquine base 300 mg administered orally as chloroquine or hydroxychloroquine once weekly. The decision of whether to offer chloroquine or hydroxychloroquine will be based on local availability.
Drug: Low-dose chloroquine/hydroxychloroquine

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

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

Other Names:
  • Aralen or Plaquenil
Experimental: Medium-dose (300mg chloroquine base twice weekly)
Chloroquine base 300 mg administered orally as chloroquine or hydroxychloroquine twice weekly. The decision of whether to offer chloroquine or hydroxychloroquine will be based on local availability.
Drug: Mid dose chloroquine or hydroxychloroquine

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

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

Other Names:
  • Aralen or Plaquenil
Experimental: High-dose (150 mg chloroquine base daily)
Chloroquine base 150 mg administered orally once daily either a chloroquine or hydroxychloroquine. The decision of whether to offer chloroquine or hydroxychloroquine will be based on local availability.
Drug: High does chloroquine or hydroxychloroquine

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

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

Other Names:
  • Aralen or Plaquenil
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 hydroxychloroquine base (or equivalent number of placebo tablets) will be taken in 4 divided daily doses (that is 300mg chloroquine or hydroxychloroquine base per day for four days) before starting the low, medium, or high dose regimen.

Open or close this module Outcome Measures
Primary Outcome Measures:
1. Symptomatic COVID-19
[ Time Frame: 3 months ]

Clinical diagnosis of COVID-19 with limitation of activities (WHO Severity Scale 2-8)
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.

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Age ≥18 years.
  2. Healthcare worker 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 'smart' mobile phone with access to the internet for data collection purposes.
  4. Participants will provide informed consent via an electronic consent process.

Exclusion Criteria:

  1. Weight outside range 50 kg - 200 kg (110 lbs - 440 lbs).
  2. Prior enrolment into this or other COVID-19 prevention or treatment trials.
  3. Self-reported, diagnosed infection with SARS-CoV-2 or previous COVID-19 diagnosis within the last 6 months.
  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. Antimalarial agents (lumefantrine, mefloquine, pyronaridine or amodiaquine), since they may cause a dangerous drug interaction.
  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; Cardiac arrhythmia; known long QTc; Psoriasis; Porphyria cutanea tarda; Epilepsy; Myasthenia gravis; Myopathy of any cause; Serious hepatic or renal disease; Severe depression; currently undergoing treatment for tuberculosis.
  9. Self-reported current use of medication with known serious hepatotoxic effects or known interaction with chloroquine
  10. Inability or unwillingness to be followed up for the trial period

NB: Pregnancy and breastfeeding are not exclusions for entry.

Open or close this module Contacts/Locations
Central Contact Person: Linda Yun, BS
Telephone: 314-273-2240
Email: lindayun@wustl.edu
Central Contact Backup: Sherry McKinnon, BS
Telephone: 314-286-1768
Email: smckinnon@wustl.edu
Study Officials: Michael S. Avidan, MBBCh
Principal Investigator
Washington Univeristy School of Medicine
Ramani Moonesinghe, MD
Principal Investigator
University College, London
Helen Rees, MD
Principal Investigator
Wits University
Locations: United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Contact:Contact: Linda Yun, BS 314-273-2240 lindayun@wustl.edu
Contact:Contact: Sherry McKinnon 314-286-1768 mckinnos@anest.wustl.edu
Contact:Principal Investigator: Michael S. Avidan, MBBCh, FCASA
Contact:Sub-Investigator: Mary Politi, MD
Contact:Principal Investigator: Eric Dubberke, MD
Australia, Victoria
Melbourne Medical School
Melbourne, Victoria, Australia, VIC 3010
Contact:Contact: David Story, MD dastory@unimelb.edu.au
Canada, Ontario
Population Health Resarch Institute
Hamilton, Ontario, Canada, L8L 2X2
Contact:Contact: Jessica Spence, MD, FRCPC spencej@phri.ca
Contact:Principal Investigator: Jessica Spence, MD, FRCPC
University of Toronto
Toronto, Ontario, Canada, M5G 1E2
Contact:Contact: David Mazer, MD (416) 864-5825 David.Mazer@unityhealth.to
Contact:Principal Investigator: David Mazer, MD
Ireland, Leinster
St James's Hospital
Dublin, Leinster, Ireland, Dublin 8
Contact:Contact: Ellen O'Sullivan, MD, FRCA,FCAI 353876993178 ellenosullivan2000@gmail.com
South Africa, Free State
Universitas Academic Hospital
Bloemfontein, Free State, South Africa, 9301
Contact:Contact: Edwin Turton, MBChB, Dip PEC, DA, MMed, FCA +27 82 804 6839 turtonew@ufs.ac.za
Contact:Principal Investigator: Edwin Turton, MBChB, Dip PEC, DA, MMed, FCA
South Africa, Gauteng
Wits RHI, University of the Witwatersrand
Johannesburg, Gauteng, South Africa, 2001
Contact:Contact: Sinead Delany-Moretlwe, MBChB, PhD, DTM&H +27 82 377 6275 sdelany@wrhi.ac.za
Contact:Contact: Michelle Moorhouse, MBChB
Contact:Sub-Investigator: Gloria Maimela, MBBCh MBA
Contact:Sub-Investigator: Saiqa Mullick, MBBCh PhD
Contact:Sub-Investigator: Catherine Martin, MBBCh MSc
Steve Biko Academic Hospital
Pretoria, Gauteng, South Africa, 0001
Contact:Contact: Sophie Mathijs, MBChB, MPharmMed +27 836506425 sandra.spijkerman@up.ac.za
Contact:Principal Investigator: Sophie Mathijs, MBChB, MPharmMed
South Africa, Western Cape
Tygerberg Hospital
Cape Town, Western Cape, South Africa, 7505
Contact:Contact: Coenraad Koegelenberg, MBChB, MMED, FCP, MRCP, PhD +27 833201307 coeniefn@sun.ac.za
Contact:Contact: Sean Chetty, MBChB, FCA, PhD
Contact:Sub-Investigator: Coenraad Koegelenberg, MBChB, MMED, FCP, MRCP, PhD
Contact: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:Contact: Laurence Lovat, MD, PhD 020 3447 7488 laurence.lovat@nhs.net
Contact:Principal Investigator: Laurence Lovat, MD, PhD
Contact:Sub-Investigator: Hakim-Moulay Dehbi, PhD
Contact:Sub-Investigator: Nick Freemantle, PhD
Contact:Sub-Investigator: Dermot McGuckin, MD
Contact:Sub-Investigator: Gemma Jones, MsC
Contact:Sub-Investigator: Ramani Moonesinghe, MD
Zambia
Centre for Infectious Disease Research in Zambia [CIDRZ]
Lusaka, Zambia, H8R9+9V
Contact:Contact: Izukanji Sikazwe
Contact:Principal Investigator: Izukanji Sikazwe
Contact:Sub-Investigator: Roma Chilengi
Contact:Sub-Investigator: Carolyn Bolton
Contact:Sub-Investigator: Chikumbutso Chipeta
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:

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