Treatment of Nosocomial COVID-19 (CATCO-NOS)

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

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.

Study Overview

• Status: Terminated
• Conditions: Covid19; SARS-CoV2 Infection; Nosocomial Infection
• Intervention / Treatment: Drug: Anti-SARS-CoV-2 mAb

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N1N4
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • Ontario
    • Ottawa, Ontario, Canada, K1K0T2
      • Hôpital Montfort
    • Toronto, Ontario, Canada, M4C3E7
      • Michael Garron Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care
Experimental: Anti SARS-CoV-2 monoclonal antibody; Single IV administration of an anti-SARS-CoV-2 Monoclonal antibody	Drug: Anti-SARS-CoV-2 mAb; 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.; Other Names: casirivimab/imdesimab, bamlanivimab, sotrovimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Sunnybrook Research Institute
• Investigators: Principal Investigator: Alain Tremblay, University of Calgary; Principal Investigator: Robert Fowler, University of Toronto; Principal Investigator: Srinivas Murthy, University of British Columbia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2021
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: bamlanivimab; casirivimab; imdesimab; sotrovimab
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Iatrogenic Disease; COVID-19; Infections; Communicable Diseases; Cross Infection; Anti-Infective Agents; Antiviral Agents; Bamlanivimab
• Other Study ID Numbers: REB21-0096

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No