Clinical trial NCT04748588: Treatment of Nosocomial COVID-19
Official title: Canadian Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of Nosocomial Acquired COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Covid19
Nosocomial Infection
SARS-CoV2 Infection
Keywords: bamlanivimab
casirivimab
imdesimab
sotrovimab
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
First posted: 2021-02-10
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants requiring mechanical ventilation or not surviving to hospital discharge
timeFrame: Length of hospitalization or 60 days
Secondary outcomes:
measure: In-hospital death
timeFrame: 60 days
measure: Need for mechanical ventilation
timeFrame: 60 days
measure: Need for new intensive care admission
timeFrame: 60 days
measure: Need for new oxygen administration
timeFrame: 60 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Ottawa
country: Canada
facility: Hôpital Montfort
state: Ontario
city: Toronto
country: Canada
facility: Michael Garron Hospital
state: Ontario
Study officials:
affiliation: University of Calgary
name: Alain Tremblay
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto
name: Robert Fowler
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Srinivas Murthy
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.