Clinical trial NCT04496245: Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85
Official title: Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Viral Infection
Covid19
Lead sponsor: The University of Queensland
Sponsor class: OTHER
Collaborators: name: Griffith University
name: The Prince Charles Hospital
name: Princess Alexandra Hospital, Brisbane, Australia
name: Telethon Kids Institute
name: Queensland Children's Hospital
First posted: 2020-08-03
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to either Group 1 (waitlist control, delayed treatment group) or Group 2 (initial treatment) for treatment for a period of 3 months with 3 months follow-up off treatment
Primary purpose: PREVENTION

Brief summary: Parallel group, Wait-list design, with treatment delayed for 3 months. Participants will be randomized on a 1:1 ratio with 500 participants per group in Australia.

Group 1: Wait-list control. One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing in Month 3, with 3 months follow-up off treatment.

Group 2: Initial treatment. One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing on day 0, with 3 months follow-up off treatment.

Detailed description: The Covid-19 pandemic has been characterised by acute respiratory distress syndrome (ARDS) accompanied by a systemic cytokine-storm resulting in severe illness, respiratory failure and death in some. Severe Acute Respiratory Syndrome (SARS)- Coronavirus (Cov-2) (COV) infection per se is not the only underlying issue here, as it is becoming evident that ARDS is relatively rare amongst infected subjects, and appears to be associated with gross dysregulation of ensuing host-anti-viral responses resulting in collateral immune-inflammatory-mediated damage to host tissues. Rather than waiting for susceptible subjects to present with COV-associated ARDS, the investigators propose treatment of healthy health care workers (HCW) with a therapeutic agent which simultaneously targets front-line innate anti-viral immune defences, together with the core mechanism that controls immune response intensity in the airways. This research addresses the hypothesis that resistance to development of severe COV-associated respiratory disease in front-line HCW, even in those who develop a primary infection, can be boosted via a regimen of daily dosing with the bacterial-derived immunomodulatory agent OM85.

Aims

1. To demonstrate that daily treatment with OM85 will prevent HCW developing acute respiratory infections (ARI) necessitating removal from the workforce.
2. To elucidate the mechanism of action by which OM85 regulates host immune responses against COV.

Mechanistic studies will primarily test the hypothesis that OM85 pre-treatment modulates the systemic immunoinflammatory response to COV, selectively attenuating potentially pathogenic pro-inflammatory pathways without compromising activation of innate immune pathways central to pathogen clearance. The investigators will additionally collect samples to test the secondary hypothesis that the host response to COV displays uniquely aggressive pro-inflammatory features that differ from those observed with non-COV respiratory infections.

Experimental design: participants will be randomised into two groups; Immediate treatment with OM85 (n=500) or wait-list control with OM85 commencing three months later (n=500). Venous blood samples will be collected from each subject at four time points. Sera will be stored from each time point for assay of COV-specific antibody. For the mechanistic studies the investigators will focus on two groups of subjects who test respectively positive or negative to COV during a defined respiratory illness. These will be further stratified by treatment (OM85 treated (OM+) versus non-treated (OM-) prior to ARI, yielding 4 sets (each n=50) of test samples collected at acute infection which will be utilized for two discrete cross-comparisons: (i) COV+/OM+ versus COV+/OM-, and (ii) COV-/OM+ versus COV-/OM-. Analyses in (i) will be prioritised as they relate exclusively to host-responses to COV and effects of treatment thereon; those in (ii) which will contrast COV-associated response with those elicited by conventional respiratory pathogens and compare respective susceptibility to OM85.

Eligibility criteria: Inclusion Criteria:

Participants who meet all of the following criteria are eligible for enrolment:

1. HCW in front line clinical departments assessing or caring for patients with suspected or verified COV infection in one of the recruiting hospitals in Brisbane
2. Participants who, in the opinion of the investigator, are able to comply with the protocol for its duration,
3. Written informed consent signed and dated according to local regulations.

Exclusion Criteria:

Participants who meet any of these criteria are not eligible for enrolment:

* Staff with prior COV infection necessitating workforce removal

Primary outcomes:
measure: Acute Respiratory Infection necessitating workforce removal
timeFrame: 3 months
Secondary outcomes:
measure: Time to ARI necessitating workforce removal.
timeFrame: 12 months
measure: The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal
timeFrame: 12 months
measure: The proportion of HCW with documented Cov infection.
timeFrame: 12 months
measure: Time to Lower respiratory infection (LRI) necessitating workforce removal.
timeFrame: 12 months
measure: The proportion of Health Care Workers contracting a LRI necessitating workforce removal
timeFrame: 12 months
measure: The proportion of HCW with documented Cov LRI.
timeFrame: 12 months
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Brisbane
country: Australia
facility: The Princess Alexandra Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
Study officials:
affiliation: The University of Queensland
name: PETER D SLY, DSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sly PD, Galbraith S, Islam Z, Holt B, Troy N, Holt PG. Primary prevention of severe lower respiratory illnesses in at-risk infants using the immunomodulator OM-85. J Allergy Clin Immunol. 2019 Sep;144(3):870-872.e11. doi: 10.1016/j.jaci.2019.05.032. Epub 2019 Jun 8. No abstract available.
citation: Esposito S, Soto-Martinez ME, Feleszko W, Jones MH, Shen KL, Schaad UB. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018 Jun;18(3):198-209. doi: 10.1097/ACI.0000000000000433.
citation: The Lancet. COVID-19: protecting health-care workers. Lancet. 2020 Mar 21;395(10228):922. doi: 10.1016/S0140-6736(20)30644-9. No abstract available.