Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection

Study Overview
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Brief Summary
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The aim of the study is to test the efficacy of the probiotic SmartProbio C in patients with a severe course of COVID-19 infection. Patients were randomly divided into two arms between the probiotic group and the placebo group. They were further divided into four groups according to 1) BMI (Body mass index; <=30/>30), 2) age (<=65/>65), 3) CRP (C-reactive protein; <=100/>100), 4) chronic lung disease (yes/no). Gut microbiome analysis and its changes in selected parameters (amount of lactobacilli, bifidobacteria, Akkermansia, Proteobacteria, Firmicutes/Bacteroidetes ratio) were chosen as the primary endpoint. Other assessed indicators include: Tracking of time to clinical improvement by two points on a seven-point ordinal scale for clinical improvement according to R&D Blueprint: COVID-19 Therapeutic Trial Synopsis (WHO, 2020) or time to hospital discharge (whichever comes first) Monitoring the length of oxygen dependence Monitoring of laboratory markers of inflammation - serum peripheral blood CRP levels Monitoring of mortality

Official Title
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A Two-arm, Double-blind, Randomized, Placebo-controlled Trial Investigating the Efficacy of the Probiotic Dietary Supplement SmartProbio C in the Supportive Supplementation of Patients With a Complicated Course of COVID-19 Infection

Conditions
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COVID-19

Intervention / Treatment
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* Dietary Supplement: SmartProbio C
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is willing and able to provide informed consent prior to any study procedure. Age at the time of screening between 18 and 85 years inclusive. Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) or immunochromatographic detection of SARS CoV-2 specific antigens no more than three days prior to randomization. COVID-19 symptoms lasting less than or equal to seven days, including. Subject is currently hospitalized and requires medical care due to COVID-19 disease and was admitted at most two days prior to randomization. Peripheral blood oxygen saturation <94% on air (as measured by pulse oximetry or arterial blood sampling) at the time of inclusion in the trial. Exclusion Criteria: Participation in any other clinical trial of an experimental treatment for COVID-19 disease. Concomitant treatment of COVID-19 with other non-standard-of-care medications less than 24 hours prior to initiation of the study intervention dosing (excluding remdesivir, corticosteroids, casirivimab, imdevimab, or bamlanivimab). Immunosuppressant treatment three months prior to hospital admission (excluding topical and inhaled corticosteroids or systemically administered corticosteroids at a dose equivalent to <40 mg Prednisone) Necessity of invasive pulmonary ventilation. Patients with known primary or secondary immunodeficiency. History of Crohn's disease or ulcerative colitis. Abnormal screening laboratory results - laboratory abnormalities that, in the opinion of the investigator, will interfere with completion of participation in the clinical trial or will interfere with the results of the trial. Participation in another clinical trial of a drug or medical device, or less than 30 days have elapsed since the completion of participation in another trial or use of the investigational drug or device. Other probiotic supplementation. Hypersensitivity to any ingredient of a product administered during a clinical trial. Women who are pregnant or breastfeeding. Patients with preterminal and terminal organ failure (COPD GOLD 3 and 4, CKD G4 and G5, NYHA 3 and 4). Any condition that, in the opinion of the investigator, may compromise the patient's ability to provide informed consent and/or comply with all required study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum<br>Patients received probiotic supplement SmartProbio C, one capsule twice a day - mornings and evenings before meal - for a period of 2 weeks. | Dietary Supplement: SmartProbio C<br>* Probiotic supplement consisting of 19 strains (Lactobacillus acidophilus NCFM, Bifidobacterium lactis, subsp. Infantis Bi-07, Lactobacillus rhamnosus LR22, Lactobacillus acidophilus LA14, Lactobacillus rhamnosus LGG, Bifidobacterium lactis HN019, Bifidobacterium lactis Bl-04, Lactobacillus acidophilus LA 11 ONLLY, Lactobacillus rhamnosus HN001, Lactobacillus plantarum LP ONLLY, Lactobacillus casei LC18, Bifidobacterium breve BB8, Lactobacillus reuteri LE16, Bifidobacterium lactis BI516, Streptococcus thermophilus ST6, Bifidobacterium animalis BA77, Bifidobacterium bifidum BB47, Bifidobacterium longum BL88 ONLLY, Bifidobacterium infantis BI211) in different ratios. Probiotic mixture enclosed in HPMC (hydroxypropylmethylcelulose) capsule, 25 billion CFU (colony-forming units) in each capsule. As a filling agent mix of inulin and maltodextrin was used. Dosage twice a day.<br>|
| Placebo Comparator: Placebo<br>Patients received placebo consisting of purified maltodextrin, one capsule twice a day - mornings and evenings before meal - for a period of 2 weeks. | Dietary Supplement: Placebo<br>* Placebo. HPMC (hydroxypropylmethylcelulose) capsule filled with maltodextrin. Dosage twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiome | Changes in selected parameters of gut microbiome (amount of lactobacilli, bifidobacteria, Akkermansia, Proteobacteria, and Firmicutes/Bacteroidetes ratio) were chosen as the primary endpoint. | The first sample was taken at the beginning of hospitalization before the start of supplementation, the second at discharge from the hospital, but not later than on the 14th day of hospitalization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospitalisation | Tracking of time to clinical improvement by two points on a seven-point ordinal scale for clinical improvement according to R&D Blueprint: COVID-19 Therapeutic Trial Synopsis (WHO, 2020), or time to hospital discharge (whichever comes first). | From the date of admission to hospital until discharge from hospital or above defined two point improvement, whichever comes first | 
| Monitoring the length of oxygen dependence | Measurement of the time it was necessary to provide HFOT (high flow oxygen therapy) to the patient | From the beginning of the provision of HFOT (high flow oxygen therapy) to the end of the provision of HFOT | 
| CRP (C-reactive protein) monitoring | Monitoring of laboratory marker of inflammation - serum peripheral blood CRP levels | On the first day of admission to hospital and on the day of hospital discharge, but no later than 14th day | 
| Monitoring mortality rates | The percentage of deaths in the placebo group compared to percentage of deaths in the verum group | From the date of admission to hospital until discharge from hospital or death, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, probiotics, probiotic supplementation