Administrative information
Title {1} | CORIPREV-LR: Study protocol for a cluster-randomized trial of post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases |
Trial registration {2a and 2b}. | This trial is registered at www.clinicaltrials.gov (NCT04321174). |
Protocol version {3} | Version 1.5, 9 June 2020 |
Funding {4} | Grant funding: Canadian Institutes of Health Research St. Michael’s Hospital Foundation In-kind support: Abbvie CIHR Centre for REACH 3.0 |
Author details {5a} | Darrell H. S. Tan,1–5 Adrienne K. Chan,3, 5, 6 Peter Jüni, 3, 5, 7 George Tomlinson,8 Nick Daneman,3, 6 Sharon Walmsley,3–5 Matthew Muller,1, 3 Rob Fowler,3, 5, 9 Srinivas Murthy,10 Natasha Press,11 Curtis Cooper,12 Todd Lee,13 Tony Mazzulli,14, 15 Allison McGeer3, 14 1. Division of Infectious Diseases, St. Michael’s Hospital 2. MAP Centre for Urban Health Solutions, St. Michael’s Hospital 3. Department of Medicine, University of Toronto 4. Division of Infectious Diseases, University Health Network 5. Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Canada 6. Division of Infectious Diseases, Sunnybrook Hospital 7. Applied Health Research Centre, St. Michael’s Hospital 8. Department of Medicine, University Health Network 9. Department of Medicine, Sunnybrook Hospital 10. Department of Pediatrics, University of British Columbia 11. Division of Infectious Diseases, St. Paul’s Hospital 12. Division of Infectious Diseases, Ottawa Hospital Research Institute 13. Division of Infectious Diseases, McGill University Health Centre 14. Department of Microbiology, Mount Sinai Hospital/University Health Network 15. Department of Laboratory Medicine and Pathobiology, University of Toronto |
Name and contact information for the trial sponsor {5b} | Sponsor-Investigator: Dr. Darrell H. S. Tan
darrell.tan@gmail.com
(416) 864-5568 |
Role of sponsor {5c} | The study funders, including those providing in-kind support for the trial, have no role in the study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. The sponsor-investigator for this trial is also the Principal Investigator, and as such is primarily responsible for the study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. The Steering Committee will have ultimate authority over all of these activities. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
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Adverse events: the proportion of participants exhibiting adverse events of any grade as defined using the DAIDS Table for Grading the Severity of Adverse Events, at 7, 14, 35, and 90 days [28].
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Symptomatic microbiologically confirmed SARS-CoV-2 infection: proportion of participants with fever, cough, or other respiratory/systemic symptoms (including but not limited to fatigue, myalgias, arthralgias, shortness of breath, sore throat, headache, chills, coryza, nausea, vomiting, diarrhea), combined with microbiologic confirmation of SARS-CoV-2 infection by PCR, by day 14.
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Seropositivity: proportion of participants with reactive serology at day 35.
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Days of hospitalization attributable to COVID-19 disease: The median number of days (or partial days) spent admitted to an acute care hospital will be tabulated both at day 35 and day 90.
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Respiratory failure requiring ventilatory support attributable to COVID-19 disease: The median number of days (or partial days) requiring (i) non-invasive or (ii) invasive ventilation will be tabulated both at day 35 and day 90.
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Mortality (proportion of participants who die) attributable to COVID-19 disease and all-cause mortality will be tabulated at 35 and 90 days.
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Health-related quality of life will be measured using the EQ-5D-5L (EuroQol-5D) (https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/). The EQ-5D consists of two pages: the EQ-5D descriptive system and the EQ visual analog scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The tool will be administered to participants at 1, 14, 35 and 90 days; the primary interest is in the median index value at 14 days.
Participant timeline {13}
Visit | Screening (day 0) | Baseline (day 1) | Day 7, ± 2 days | Day 14, ± 2 days | Day 35, ± 4 days | Day 90, ± 2 days |
---|---|---|---|---|---|---|
Visit format | Remote | Remote | Remote | Remote | In person | Remote |
Eligibility assessment | X | |||||
Informed consent/assent | X | |||||
Cluster randomization | Xa | |||||
Dispensation of study drug (LPV/r arm) | X | |||||
Interview by study staff | X | X | X | X | X | |
Concomitant medication assessment | X | X | X | X | X | |
Adverse event assessment | X | X | X | X | ||
Adherence diary (LPV/r arm) | Daily on d1–14 | |||||
Symptom diary | Daily on d2–15, then d21, d28, d35 | |||||
Temperature diary | Daily on d1–14 | |||||
Visit-specific questionnaireb | X | X | X | X | ||
HIV self-testc | X | |||||
Self-collected saliva sample | X | X | X | X | ||
Self-collected oropharyngeal/nasal swabd | X | X | X | |||
Self-collected dried blood spot | Xe | Xf | ||||
Blood for SARS-CoV-2 serology | Xg | X | ||||
Stored blood samples | X | |||||
Blood for CBC | Xf |
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Confidentiality {27}
Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
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Symptomatic COVID-19 disease by day 14
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Seropositivity by day 35
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Days of hospitalization attributable to COVID-19 disease by day 90
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Respiratory failure attributable to COVID-19 disease requiring (i) non-invasive and (ii) invasive ventilation by day 90
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Mortality attributable to COVID-19 disease
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Health-related quality of life, measured by the EQ-5D-5 L on days 1, 14, 35, and 90
Interim analyses {21b}
Methods for additional analyses (e.g., subgroup analyses) {20b}
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Plans to give access to the full protocol, participant level-data and statistical code {31c}
Oversight and monitoring
Composition of the coordinating center and trial steering committee {5d}
Composition of the data safety monitoring board, its role and reporting structure {21a}
Adverse event reporting and harms {22}
Frequency and plans for auditing trial conduct {23}
Plans for communicating important protocol amendments to relevant parties (e.g., trial participants, ethical committees) {25}
Dissemination plans {31a}
Discussion
Trial status
Acknowledgements
Name | Institution | City |
---|---|---|
Adrienne Chan | Sunnybrook Health Sciences Centre | Toronto |
Bryan Coburn | University of Toronto | Toronto |
Curtis Cooper | The Ottawa Hospital | Ottawa |
Nick Daneman | Sunnybrook Health Sciences Centre | Toronto |
Robert Fowler | Sunnybrook Health Sciences Centre | Toronto |
Jennifer Gommerman | University of Toronto | Toronto |
Chris Graham | Trillium Health Partners | Toronto |
Rebecca Hancock-Howard | University of Toronto | Toronto |
Peter Juni | University of Toronto | Toronto |
Todd Lee | McGill University Health Centre | Montreal |
Jerome Leis | Sunnybrook Health Sciences Centre | Toronto |
Robert Maunder | Mount Sinai Hospital | Toronto |
Tony Mazzulli | Mount Sinai Hospital | Toronto |
Janine McCready | Michael Garron Hospital | Toronto |
Allison McGeer | Mount Sinai Hospital | Toronto |
Samira Mubareka | Sunnybrook Health Sciences Centre | Toronto |
Matthew Muller | St. Michael’s Hospital | Toronto |
Srinivas Murthy | University of British Columbia | Vancouver |
Mark Naccarato | St Michael’s Hospital | Toronto |
Braden O’Neill | North York General Hospital | Toronto |
Andrew Pinto | St Michael’s Hospital | Toronto |
Natasha Press | St. Paul’s Hospital | Vancouver |
Attia Qamar | St Michael’s Hospital | Toronto |
Herveen Sachdeva | Toronto Public Health | Toronto |
So-Yan Seto | Toronto Public Health | Toronto |
Darrell Tan | St. Michael’s Hospital | Toronto |
George Tomlinson | University Health Network | Toronto |
Sharon Walmsley | University Health Network | Toronto |
Deborah Yoong | St Michael’s Hospital | Toronto |