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CROWN CORONATION: COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION (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 : Recruiting
First Posted : April 3, 2020
Last Update Posted : September 9, 2020
Sponsor:
Collaborator:
COVID -19 Therapeutics Accelerator
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 September 9, 2020
Actual Study Start Date  ICMJE September 4, 2020
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2020)
Symptomatic COVID-19 [ Time Frame: 60 days ]
To determine the incidence of the trial intervention(s) in preventing laboratory test-confirmed, symptomatic COVID19 (i.e. any of the following: cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, nausea, vomiting, or diarrhea), in healthcare workers with repeated exposures to SARS-CoV-2 by day 60 after enrollment.
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
 (submitted: August 4, 2020)
  • Severity of COVID-19 over the study period [ Time Frame: 60 days ]
    Severity of COVID-19 will be graded on a simplified version of the ordinal World Health Organization COVID-19 severity scale (WHO COVID-19 severity scale).
  • Effectiveness of preventing/reducing SARS-CoV-2 infection [ Time Frame: 5 months ]
    SARS-CoV-2 infection (by serology) over up to 5 months of follow-up
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: COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION
Official Title  ICMJE An International, Multi-site, Bayesian Platform Adaptive, Randomized, Placebo-controlled Trial Assessing the Effectiveness of Candidate Agents in Mitigating COVID-19 Disease in Healthcare Workers
Brief Summary The objective of CROWN CORONATION is the prevention of symptomatic COVID-19 by using combinations of approved and safe repurposed interventions, with complementary mechanisms of action.
Detailed Description

CROWN CORONATION is an international, Bayesian platform adaptive, randomized, placebo-controlled trial assessing the effectiveness of candidate interventions in preventing COVID-19 disease in healthcare workers.

Randomization will be stratified by age (<50 and ≥50) and site. Participants will be healthcare workers at risk of contracting SARS-CoV-2. Participants will be randomized into one of two arms:

  • Education and surveillance plus MR or MMR vaccine
  • Education and surveillance plus Placebo

While the initial intervention to be tested on the platform will be the MR or MMR vaccine, other interventions might be added or removed over the course of the trial. The trial will evaluate which of the intervention arms is most effective at decreasing the incidence of symptomatic COVID-19 disease, without unacceptable side effects or safety events.

All participants will require be required to have a mobile phone to participate. This is standard in all the countries in this study. Most, but not all, will also have a smartphone. Participants will complete weekly data logs via SMS texting. Follow-up information will be collected until approximately 5 months after the end of treatment or death. Participants who develop symptomatic COVID-19 during the last month of observation will at a minimum be followed-up until symptom resolution and at a maximum until 6 months after randomization (whichever comes first). Telemedicine approaches to collecting information on participants will be used where possible. The trial will provide adherence support interventions that have been shown in randomized controlled trials to improve adherence to Human Immunodeficiency Virus treatment and adapted for HIV Pre-Exposure Prophylaxis (HIV PrEP) (e.g. two-way SMS with check in for those that report symptoms or adverse events). The database will be hosted on UK-based servers which are expected to be managed by Sealed Envelope Ltd. Local investigators will have access to the part of the CRF to enable recording of outcome data and/or severity of COVID-19 symptoms. Participants will be given a secure login to enable them to complete an initial participant health questionnaire and the regular data logs. It is envisaged that these will be completed at least weekly.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
An international, multi-site, randomized, placebo-controlled, Bayesian platform clinical trial. Initially there will be 2 arms, but we anticipate adding intervention arms to the platform. Combining interventions, allowing assessment of potential interactions, will be considered when arms are added.
Masking: Double (Participant, Investigator)
Masking Description:
For the MR or MMR vaccine, there will be a placebo vaccine. Attempts will be made to maintain masking for other interventions (e.g. oral tablets) added to the platform by including suitable placebo options.
Primary Purpose: Prevention
Condition  ICMJE COVID 19
Intervention  ICMJE
  • Drug: MR or M-M-R II ® vaccine
    Education and surveillance plus MR or M-M-R II ® vaccine
    Other Name: Merck
  • Drug: Placebo
    Placebo injection
Study Arms  ICMJE
  • Experimental: M-M-R II ®
    Education and surveillance plus M-M-R II ®
    Intervention: Drug: MR or M-M-R II ® vaccine
  • Placebo Comparator: Placebo
    Education and surveillance plus placebo
    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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 4, 2020)
30000
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2020)
55000
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 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. Prior enrollment into other COVID-19 interventional prevention or treatment trials (observational trials not excluded).
  2. Self-reported or diagnosed current infection with SARS-CoV-2 or previous COVID-19 diagnosis.
  3. Self-reported current acute respiratory infection.
  4. Concurrent and/or recent involvement in other research or use of the investigational product, a product considered to be equivalent to the investigational product, or any other product that is likely to interfere with the investigational products in this trial used within three months of study enrolment.
  5. Self-reported known allergies to any of the IMPs and excipients of the IMPs and placebo.
  6. Self-reported presence or history of the conditions listed in the appendices.
  7. Self-reported current use of medication known to interact with any of the medications listed in the appendices.
  8. Inability or unwillingness to be followed up for the trial period.

For M-M-R II

  • Pregnant women.
  • Individuals receiving high dose corticosteroids, other immuno-suppressive drugs, alkylating agents or anti-metabolites.
  • Individuals undergoing radiotherapy.
  • Any malignant disease either untreated or currently undergoing therapy.
  • History of administration of gammaglobulin or blood transfusions within the previous 3 months.
  • Participants with an allergy to the MR (MMR) vaccine or its components, including neomycin.
  • Idiopathic thrombocytopenic purpura (ITP)
  • Untreated tuberculosis
  • Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrollment
  • Planned receipt of any vaccine other than the study intervention within 30 days before and after the study vaccination
  • Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including untreated HIV infection with a CD4T count <200 /mL
  • Asplenia
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, CCRP 314-273-2240 crowntrial@email.wustl.edu
Contact: Sherry McKinnon, MS, CCRP 314-286-1768 crowntrial@email.wustl.edu
Listed Location Countries  ICMJE Canada,   Ghana,   Ireland,   Netherlands,   South Africa,   Uganda,   United Kingdom,   United States,   Zambia,   Zimbabwe
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT04333732
Other Study ID Numbers  ICMJE 202004099
INV-017499 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
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 COVID -19 Therapeutics Accelerator
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 September 2020

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