Treatment of Nosocomial COVID-19

Study Overview
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Brief Summary
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COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. Nosocomial acquisition of SARS-CoV-2 is a frequent concern across hospital settings in Canada and is associated with substantial morbidity and mortality. This clinical trial is initially designed to evaluate the role of monoclonal antibodies against the SARS-CoV-2 spike protein, for the treatment of hospitalized patients who acquire COVID19 via nosocomial infection. New treatments, as they become available, may be integrated, with appropriate adaptation of this document. The trial was initiated with the bamlanivimab product with the options of casirivimab/imdesimab and sotrovimab added as the prevalence of bamlanivimab resistant variants of concerns increased. It is believed that monoclonal antibody treatments are most likely to be effective early in the disease course. The ability to rapidly identify and initiate such treatments in patients with nosocomial acquisition of the infection, combined with the high mortality of 25-30% experienced by this group of patients led us to propose this trial in collaboration with the CATCO national network. The overall objective of the study is to evaluate the safety and clinical effectiveness of anti-SARS-CoV-2 monoclonal antibody treatment relative to the control arm, in patients who develop nosocomial SARS-CoV-2 infection, on need for mechanical ventilation or death. This study is designed as a pragmatic randomized, open-label, controlled clinical trial. Subjects will be randomized to receive either standard-of-care (control) or the study medication on a 1:2 basis. Bamlanivimab, casirivimab/imdesimab or sotrovimab will be administered intravenously as a one-time infusion after randomization. Casirivimab/imdesimab (REGN) and sotrovimab will be the default agents based on local availability unless both are unavailable AND virus strain known to be native or alpha (B.1.1.7). Incidence of infusion-related reactions in the 24 hours post administration.

Official Title
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Canadian Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of Nosocomial Acquired COVID-19 Patients

Conditions
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Covid19, Nosocomial Infection, SARS-CoV2 Infection

Intervention / Treatment
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* Drug: Anti-SARS-CoV-2 mAb


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay, in any specimen prior to randomization. Admitted to a participating centre Is nosocomially acquired infection, as defined by ALL of: COVID19 diagnosis being made on admission day three or later; Admitted for a reason other than COVID19; Within 5 days of COVID19 diagnosis based on test collection date or initial development of symptoms, which ever was earliest. Exclusion Criteria: Plan for palliation within 24 hours Known allergy to study medication or its components (non-medicinal ingredients) Ordinal scale 6 or above Admitted to facility for non-medical reasons including primary psychiatric diagnosis or labour and delivery. Pregnancy or breast feeding Weight less than 40kg

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of care<br> | |
| Experimental: Anti SARS-CoV-2 monoclonal antibody<br>Single IV administration of an anti-SARS-CoV-2 Monoclonal antibody | Drug: Anti-SARS-CoV-2 mAb<br>* Casirivimab/imdesimab 1200mg/1200mg OR sotrovimab 500mg OR bamlanivimab 700mg IV x1. Casirivimab/imdesimab (REGN) and sotrovimab will be the default agents used (according to local availability) unless both unavailable AND virus strain known to be native or alpha (B.1.1.7) in which case bamlanivimab can be used.<br>* Other names: casirivimab/imdesimab, bamlanivimab, sotrovimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants requiring mechanical ventilation or not surviving to hospital discharge |  | Length of hospitalization or 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital death |  | 60 days | 
| Need for mechanical ventilation |  | 60 days | 
| Need for new intensive care admission |  | 60 days | 
| Need for new oxygen administration |  | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bamlanivimab, casirivimab, imdesimab, sotrovimab