Beta-glucans for Hospitalised Patients With COVID-19

Study Overview
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Brief Summary
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This randomised trial aims to assess the role of beta1-3 glucan supplementation in improving clinical symptoms and other outcomes amongst hospitalised patients with COVID-19.

Detailed Description
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COVID-19 can present as a life-threatening disease characterised by respiratory failure and high circulating levels of inflammatory cytokines. Beta-glucans comprise a heterogeneous group of natural polysaccharides consisting of D-glucose monomers linked by a beta-glycosidic bond. They represent key structural elements of the cell wall and may serve as energy storage in bacteria, fungi including yeast, algae, and plants. In this triple-masked randomised trial, hospitalised patients requiring treatment with supplemental oxygen because of a laboratory-confirmed infection by SARS-CoV-2 will receive supplementation with 1-3 beta-glucans or placebo as part of their standard treatment. The primary endpoint of this trial is the intensity of clinical symptoms as detected by the Wisconsin Upper Respiratory Symptom Survey (WURSS). Patients requiring mechanical ventilation at baseline will be excluded, as will those with cognitive impairment that precludes the use of clinical assessment scales, patients in which an order to limit therapeutic efforts has been issued, pregnant or breastfeeding women and those who decline to participate in this study. Secondary outcomes will include clinical deterioration requiring admission to an intensive care unit, requirement of high-flow nasal cannula or invasive mechanical ventilation and overall survival. Patients will be followed-up until hospital discharge or up to fifteen days after randomisation. Statistical analyses will be undertaken by a statistician unaware of treatment allocation under the intention-to-treat principle.

Official Title
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Beta-glucans as Immune Modulators Amongst Hospitalised Patients With COVID-19: A Pilot Randomised Trial

Conditions
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COVID-19

Intervention / Treatment
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* Drug: MC 3x3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants with an infection caused by SARS-CoV-2 confirmed with a reverse-transcription polymerase chain reaction (RT-PCR) obtained from a nasopharyngeal swab. Exclusion Criteria: Life expectancy < 6 months Currently receiving invasive mechanical ventilation at baseline. Cognitive impairment that precludes the use of WURSS or understanding the informed consent form. Refusal to participate.

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
Interventional Model Description: Eligible participants will be randomised to receive either beta-glucan supplements or placebo for up to three days.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta-Glucans<br>Patients allocated to this arm will receive MC 3x3, an oral supplement containing 25mg of 1,3 beta-Glucans daily for up to three consecutive days. | Drug: MC 3x3<br>* Patients allocated to this arm will receive MC 3x3, an oral supplement containing 25mg of 1,3 beta-Glucans of fungal origin (Trichoderma sp.) daily for up to three consecutive days.<br>|
| Placebo Comparator: Placebo<br>Participants allocated to this arm will receive a placebo that will be identical in form to the MC 3x3 pills used the interventional arm. These doses will be scheduled daily and administered orally for up to three consecutive days. | Drug: Placebo<br>* Patients allocated to this arm will receive a matching placebo similar to MC 3x3 pills used in the intervention arm. Placebos will be delivered orally every day for up to three consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom severity | Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score. | WURSS-21 scores calculated 1 day after randomisation | 
| Symptom severity | Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score. | WURSS-21 scores calculated 2 days after randomisation | 
| Symptom severity | Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score. | WURSS-21 scores calculated 3 days after randomisation | 
| Symptom severity | Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score. | WURSS-21 scores calculated 5 days after randomisation | 
| Symptom severity | Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score. | WURSS-21 scores calculated 7 days after randomisation | 
| Symptom duration | Total time with disease manifestations attributable to COVID-19. | Up to 2 weeks after randomisation or hospital discharge | 
| Clinical recovery | Number of patients without clinical complaints attributable to COVID-19 | Seven days after randomisation or up to hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-Reactive protein levels | C-Reactive protein levels measured at various time intervals during the hospitalisation. | This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation. | 
| Absolute lymphocyte count | Absolute lymphocyte counts measured at various time intervals during the hospitalisation. | This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation. | 
| Neutrophil to lymphocyte ratio | Neutrophil to lymphocyte ratios measured at various time intervals during the hospitalisation. | This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation. | 
| Intensive Care Unit Admission | Proportion of patients requiring admission to an intensive care unit in each study group | Up to seven days after randomisation | 
| Invasive mechanical ventilation | Proportion of patients requiring invasive mechanical ventilation in each study group | Up to seven days after randomisation | 
| Survival | Proportion of patients that survived COVID-19 in each study group | Up to seven days after randomisation | 
| Hospital Stay | Total stay within the hospital amongst participants | Until hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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beta-Glucans, Therapy, Signs and Symptoms, Mechanical ventilation, Inflammation, Survival