Treatment of Nosocomial COVID-19

NCT04748588 | Terminated Phase 4 DMC

• 1 other identifier: REB21-0096
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 4

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.

Conditions

Covid19; Nosocomial Infection; SARS-CoV2 Infection

Keywords

bamlanivimab; casirivimab; imdesimab; sotrovimab

Outcome Measures

Primary Outcomes (1)

• Proportion of participants requiring mechanical ventilation or not surviving to hospital discharge

  Length of hospitalization or 60 days

Secondary Outcomes (4)

• 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

Study Arms (2)

Standard of care

NO INTERVENTION

Anti SARS-CoV-2 monoclonal antibody

EXPERIMENTAL

Single IV administration of an anti-SARS-CoV-2 Monoclonal antibody

Drug: Anti-SARS-CoV-2 mAb

Interventions

Anti-SARS-CoV-2 mAb DRUG

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.

Also known as: casirivimab/imdesimab, bamlanivimab, sotrovimab

Anti SARS-CoV-2 monoclonal antibody

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Sunnybrook Research Institute: collaborator

Study Sites (4)

University of Calgary

Calgary, Alberta, T2N1N4, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Hôpital Montfort

Ottawa, Ontario, K1K0T2, Canada

Location

Michael Garron Hospital

Toronto, Ontario, M4C3E7, Canada

Location

Related Publications (1)

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19; Cross Infection

Interventions

casirivimab; bamlanivimab; sotrovimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alain Tremblay

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Robert Fowler

  University of Toronto

  PRINCIPAL INVESTIGATOR

• Srinivas Murthy

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 10, 2021
• Study Start: February 12, 2021
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2022
• Last Updated: April 19, 2023

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)