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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04333732




Registration number
NCT04333732
Ethics application status
Date submitted
31/03/2020
Date registered
3/04/2020
Date last updated
15/04/2020

Titles & IDs
Public title
CROWN CORONATION: Chloroquine RepurpOsing to healthWorkers for Novel CORONAvirus mitigaTION
Scientific 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 ID [1] 0 0
202004099
Universal Trial Number (UTN)
Trial acronym
CROWN CORONA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID 19 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Low-dose chloroquine/hydroxychloroquine
Treatment: Drugs - Mid dose chloroquine or hydroxychloroquine
Treatment: Drugs - High does chloroquine or hydroxychloroquine
Treatment: Drugs - Placebo

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.

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.

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Symptomatic COVID-19 - Clinical diagnosis of COVID-19 with limitation of activities (WHO Severity Scale 2-8)
Timepoint [1] 0 0
3 months
Primary outcome [2] 0 0
Peak severity of COVID-19 over the study period - 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.
Timepoint [2] 0 0
3 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Melbourne Medical School - Melbourne
Recruitment postcode(s) [1] 0 0
VIC 3010 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Missouri
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Ireland
State/province [3] 0 0
Leinster
Country [4] 0 0
South Africa
State/province [4] 0 0
Free State
Country [5] 0 0
South Africa
State/province [5] 0 0
Gauteng
Country [6] 0 0
South Africa
State/province [6] 0 0
Western Cape
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London
Country [8] 0 0
Zambia
State/province [8] 0 0
Lusaka

Funding & Sponsors
Primary sponsor type
Other
Name
Washington University School of Medicine
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Bill and Melinda Gates Foundation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04333732
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael S. Avidan, MBBCh
Address 0 0
Washington Univeristy School of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Linda Yun, BS
Address 0 0
Country 0 0
Phone 0 0
314-273-2240
Fax 0 0
Email 0 0
lindayun@wustl.edu
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04333732