Coronavirus InfectionNCT04854941
Efficacy of Probiotics in the Treatment of Hospitalised Patients With Novel Coronavirus Infection
A study testing Probiotics in people with Coronavirus Infection, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
Trial summary
The treatment of the new coronavirus infection (COVID-19) and COVID-19-associated diarrhoea and liver injury remains challenging. Optimizing treatment approaches for COVID-19 remains an issue. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coronavirus Infection
- What is being tested?
- Probiotics
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteRussia
- Study dates
- 10 Dec 2020to 10 Apr 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with COVID-19 infection confirmed by polymerase chain reaction of nasopharyngeal and oropharyngeal swabs to the causative agent of this infection
- age from 18 to 75 years old from December 2020 to April 2021
Who cannot join
- the patient's decision to withdraw from the study
- refusing to take the probiotic for a reason not related to the development of side effects.
- Non-inclusion criteria:
- age over 75 years old or under 18 years old,
- taking probiotics for 3 months prior to admission
- history of intolerance to probiotics or their components
Show all 11Show fewer
- refusal to participate and sign informed consent
- pregnancy or breastfeeding
- presence of cancer or psychoemotional disorders
- renal failure at the time of admission (glomerular filtration rate less than 50 ml / min)
- hepatic failure at the time of admission (equivalent to cirrhosis class B or C on the Child-Pugh scale)
Trial locations and contacts
1 site in 1 country.
Russia1 site
I.M. Sechenov First Moscow State Medical University
Moscow, 119991
About this study
Official title: Efficacy of Probiotics (Lactobacillus Rhamnosus, Bifidobacterium Bifidum, Bifidobacterium Longum Subsp. Infantis and Bifidobacterium Longum) in the Treatment of Hospitalised Patients With Novel Coronavirus Infection
The treatment of the new coronavirus infection (COVID-19) and COVID-19-associated diarrhoea and liver injury remains challenging. Optimizing treatment approaches for COVID-19 remains an issue. It is assumed, that changes in composition of intestinal microbiota is closely related to a change in the regulation of the immune response in the lungs in patients with COVID-19. These gut microbiota changes in combination with antibiotic prescription during the treatment increase the risk of antibiotic-associated diarrhea and C. difficile infection as well as worse clinical outcomes in these patients. Probiotics are useful for restoring the human gut microbiome and increasing anti-inflammatory response also. Despite the variety of uses of probiotics, there is still insufficient data on the clinical efficacy of including probiotics in the treatment of patients with COVID-19 infection.
Read the detailed description
A randomized controlled open-label study approved by the local ethical committee. The study included patients with COVID-19 admitted to the T.M. Tareev Clinic of Internal Diseases of I.M. Sechenov First Moscow State Medical University in whom the disease was confirmed using polymerase chain reaction on nasopharyngeal and oropharyngeal swabs to detect severe acute respiratory syndrome-related coronavirus 2 (SARS-COV-2). The study was conducted from December 2020 to March 2021 and included participants in the age range from 18 to 75 years.
The exclusion criteria were age over 75 years or under 18 years, consumption of probiotics for 3 months prior to admission, history of intolerance to probiotics or their components, refusal to participate and sign informed consent, pregnancy or breastfeeding, cancer or mental illness, and severe renal (glomerular filtration rate less than 50 mL/min) or hepatic (equivalent to cirrhosis class B or C on the Child-Pugh scale) dysfunction at the time of admission.
Patients who prematurely discontinued the consumption of probiotics for reasons not related to the development of side effects were excluded from the study.
The patients were randomised to the probiotics group (PRO group) or the control group (CON group). Patients in the PRO group received probiotics containing ~109 colony forming units (CFU) of Lactobacillus rhamnosus PDV 1705, ~109 CFU of Bifidobacterium bifidum PDV 0903, ~109 CFU of B. longum subsp. infantis PDV 1911, and ~109 CFU of B. longum PDV 2301 three times a day during the hospital stay but for no more than 14 days (PDV is the commercial letter designation of the bacterial strains). The end point of the trial was day 14 of hospitalisation or the day of the patient's discharge or death, whichever occurred earlier.
The control group consisted of patients who did not receive probiotics. Patients in both the groups also received dexamethasone and antiviral (favipiravir and/or riamilovir), antibacterial, anticoagulant (enoxaparin in most cases; rivaroxaban and dabigatran were used much less frequently), and anticytokine (tocilizumab or/and olokizumab) drugs according to indications and contraindications.
Death from any cause was considered the primary outcome. Duration of hospitalisation, total duration of the disease, incidence of admission to intensive care unit, need for oxygen support or mechanical ventilation, and changes in the values of key biomarkers were considered the main secondary outcomes. The duration of diarrhoea [loose or watery stools or an increase in the frequency of bowel movements (more than three times per day)] and incidence of hospital-acquired diarrhoea as well as the progression of pre-existing liver injury and onset of liver injury were considered additional secondary outcomes. Liver injury was determined through the presence of abnormalities in any of the main liver test findings (serum alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, and albumin levels).
The volume of the affected lungs was measured using chest computed tomography (CT); it included the sum of ground glass and consolidation volumes.
Results are presented as the median [interquartile range]. The groups were compared using Mann-Whitney test for continuous data and chi-square test for categorical data. Wilcoxon test was used to assess the changes in continuous biomarker values. Mortality was assessed using the Kaplan-Meier estimator and Cox's test. A p value ≤0.05 was considered the criterion for significance. Statistical calculations were performed using "Statistica 10" soft (TIBCO Software inc, Palo Alto, CA)
- Conditions
- Coronavirus Infection
- Being tested
- Probiotics
- Keywords
- Novel Coronavirus Infection, Probiotics, Lactobacillus, Bifidobacterium, Clinical outcomes, C.difficile, Diarrhea, Liver, mortality
- Medical subject headings
- Coronavirus Infections, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticsOther
Probiotics (10^9 CFU of each strain: Lactobacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911 and Bifidobacterium longum PDV 2301) 3 times per day in addition to standard treatment regimen for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Probiotics group (PRO) | Experimental | 99 patients with COVID-19 infection who have been supplemented with a Lactobacillus and Bifidobacterium containing probiotic in addition to standard regimen (oxygen support, antiviral, antibacterial, anticoagulant, anticytokine (tocilizumab and olokizumab) drugs and dexamethasone treatment according to indications and contraindications) Receives: Other: Probiotics |
| Control group (CON) | No intervention | 101 patients with COVID-19 infection who have been treated with standard regimen only (oxygen support, antiviral, antibacterial, anticoagulant, anticytokine (tocilizumab and olokizumab) drugs and dexamethasone treatment according to indications and contraindications) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
The number of died patients during hospitalization
Measured: During hospitalization (Since the first day of hospitalization to the day of the patient's discharge)
Secondary outcomes (24)
Duration of hospitalization
The number of days patients stayed at hospital
Measured: Since the first day of hospitalization to the day of the patient's discharge
Total duration of the disease
The number of days patients had complaints
Measured: Since the first day of hospitalization to the day of the patient's discharge
Incidence of admission to intensive care unit
The number of patients admitted to the intensive care unit during hospitalization
Measured: at the 14th day of hospitalization or at the day of the patient's discharge
Need for non-invasive ventilation
The number of patients requiring a non-invasive ventilation during hospitalization
Measured: at the 14th day of hospitalization or at the day of the patient's discharge
Days of non-invasive ventilation
The number of days that patients had non-invasive ventilation during hospitalization
Measured: at the 14th day of hospitalization or at the day of the patient's discharge
Need for invasive ventilation
The number of patients requiring an invasive ventilation during hospitalization
Measured: at the 14th day of hospitalization or at the day of the patient's discharge
Changes in the values of C-reactive protein level in serum
The values of C-reactive protein level (mg/L) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of white blood cells in blood test
The counts of white blood cells (10^9/L) in blood test of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of neutrophils in blood test
The counts of neutrophils (10^9/L) in blood test of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of lymphocytes
The counts of lymphocytes (10^9/L) in blood test of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of platelets
The counts of platelets (10^9/L) in blood test of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of erythrocyte sedimentation rate in in blood test
The values of erythrocyte sedimentation rate (mm/hr) in blood test of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of creatinine level in serum
The values of creatinine (μmol/l) level in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of alanine aminotransferase (ALT) level in serum
The values of alanine aminotransferase (ALT) level (u/L) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of aspartate aminotransferase level in serum
The values of aspartate aminotransferase (AST) level (u/L) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of albumen level in serum
The values of albumen level (g/L) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of total bilirubin level in serum
The values of total bilirubin level (μmol/l) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of lactate dehydrogenase level in serum
The values of lactate dehydrogenase (LDH) level (u/l) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of ferritin level in serum
The values of ferritin level (μg/l) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of fibrinogen level in serum
The values of fibrinogen level (g/l) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of potassium level in serum
The values of potassium level (mmol/l) in serum of the patients during hospitalization
Measured: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Incidence of diarrhoea
The number of patients with diarrhea (loose or watery stools or frequent bowel movements more than three times a day) during hospitalization
Measured: at 14th day of hospitalization (or at the day of the patient's discharge)
The duration of diarrhoea
The number of days that the patients had diarrhea (loose or watery stools or frequent bowel movements more than three times a day)
Measured: at 14th day of hospitalization (or at the day of the patient's discharge)
The maximum volume of the affected lungs
The volume of the affected lungs counted by the sum of ground glass and consolidation volumes (%) using chest computed tomography (CT)
Measured: at 14th day of hospitalization (or at the day of the patient's discharge)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start10 Dec 2020
- Primary completion10 Mar 2021
- Study completion10 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Coronavirus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.M. Sechenov First Moscow State Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04854941
- Sponsor's protocol ID
- PROCOV-19-2020
- Status last verified
- Apr 2021
- First submitted
- 7 Apr 2021
- Last updated
- 28 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The provision of data is prohibited by Local Ethical Committee and is possible upon receipt of an official request addressed to the principal investigator
Publications
Madabhavi I, Sarkar M, Kadakol N. COVID-19: a review. Monaldi Arch Chest Dis. 2020 May 14;90(2). doi: 10.4081/monaldi.2020.1298.
PubMed 32498503Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, Dzharullaeva AS, Grousova DM, Erokhova AS, Kovyrshina AV, Botikov AG, Izhaeva FM, Popova O, Ozharovskaya TA, Esmagambetov IB, Favorskaya IA, Zrelkin DI, Voronina DV, Shcherbinin DN, Semikhin AS, Simakova YV, Tokarskaya EA, Lubenets NL, Egorova DA, Shmarov MM, Nikitenko NA, Morozova LF, Smolyarchuk EA, Kryukov EV, Babira VF, Borisevich SV, Naroditsky BS, Gintsburg AL. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020 Sep 26;396(10255):887-897. doi: 10.1016/S0140-6736(20)31866-3. Epub 2020 Sep 4.
PubMed 32896291Tariq R, Saha S, Furqan F, Hassett L, Pardi D, Khanna S. Prevalence and Mortality of COVID-19 Patients With Gastrointestinal Symptoms: A Systematic Review and Meta-analysis. Mayo Clin Proc. 2020 Aug;95(8):1632-1648. doi: 10.1016/j.mayocp.2020.06.003. Epub 2020 Jun 10.
PubMed 32753138Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, Khare S, Srivastava A. Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis. Indian J Gastroenterol. 2020 Jun;39(3):268-284. doi: 10.1007/s12664-020-01058-3. Epub 2020 Aug 4.
PubMed 32749643Rokkas T. Gastrointestinal involvement in COVID-19: a systematic review and meta-analysis. Ann Gastroenterol. 2020 Jul-Aug;33(4):355-365. doi: 10.20524/aog.2020.0506. Epub 2020 Jun 6.
PubMed 32624655Zarifian A, Zamiri Bidary M, Arekhi S, Rafiee M, Gholamalizadeh H, Amiriani A, Ghaderi MS, Khadem-Rezaiyan M, Amini M, Ganji A. Gastrointestinal and hepatic abnormalities in patients with confirmed COVID-19: A systematic review and meta-analysis. J Med Virol. 2021 Jan;93(1):336-350. doi: 10.1002/jmv.26314. Epub 2020 Jul 27.
PubMed 32681674Suresh Kumar VC, Mukherjee S, Harne PS, Subedi A, Ganapathy MK, Patthipati VS, Sapkota B. Novelty in the gut: a systematic review and meta-analysis of the gastrointestinal manifestations of COVID-19. BMJ Open Gastroenterol. 2020 May;7(1):e000417. doi: 10.1136/bmjgast-2020-000417.
PubMed 32457035Sultan S, Altayar O, Siddique SM, Davitkov P, Feuerstein JD, Lim JK, Falck-Ytter Y, El-Serag HB; AGA Institute. Electronic address: ewilson@gastro.org. AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19. Gastroenterology. 2020 Jul;159(1):320-334.e27. doi: 10.1053/j.gastro.2020.05.001. Epub 2020 May 11.
PubMed 32407808Wang H, Qiu P, Liu J, Wang F, Zhao Q. The liver injury and gastrointestinal symptoms in patients with Coronavirus Disease 19: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2020 Oct;44(5):653-661. doi: 10.1016/j.clinre.2020.04.012. Epub 2020 May 12.
PubMed 32418852Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, Shen J, Zhu LR, Chen Y, Iacucci M, Ng SC, Ghosh S, Chen MH. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020 Jul;5(7):667-678. doi: 10.1016/S2468-1253(20)30126-6. Epub 2020 May 12.
PubMed 32405603Bottari B, Castellone V, Neviani E. Probiotics and Covid-19. Int J Food Sci Nutr. 2021 May;72(3):293-299. doi: 10.1080/09637486.2020.1807475. Epub 2020 Aug 12.
PubMed 32787470Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.
PubMed 32085846Spigaglia P. COVID-19 and Clostridioides difficile infection (CDI): Possible implications for elderly patients. Anaerobe. 2020 Aug;64:102233. doi: 10.1016/j.anaerobe.2020.102233. Epub 2020 Jun 25.
PubMed 32593567d'Ettorre G, Ceccarelli G, Marazzato M, Campagna G, Pinacchio C, Alessandri F, Ruberto F, Rossi G, Celani L, Scagnolari C, Mastropietro C, Trinchieri V, Recchia GE, Mauro V, Antonelli G, Pugliese F, Mastroianni CM. Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19. Front Med (Lausanne). 2020 Jul 7;7:389. doi: 10.3389/fmed.2020.00389. eCollection 2020.
PubMed 32733907Ivashkin V, Fomin V, Moiseev S, Brovko M, Maslennikov R, Ulyanin A, Sholomova V, Vasilyeva M, Trush E, Shifrin O, Poluektova E. Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial. Probiotics Antimicrob Proteins. 2023 Jun;15(3):460-468. doi: 10.1007/s12602-021-09858-5. Epub 2021 Oct 13.
PubMed 34643888
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Probiotics (Lactobacillus Rhamnosus, Bifidobacterium Bifidum, Bifidobacterium Longum Subsp. Infantis and Bifidobacterium Longum) in the Treatment of Hospitalised Patients With Novel Coronavirus Infection
- ClinicalTrials.gov ID
- NCT04854941
- Acronym / sponsor ID
- PROCOV-19-2020
- Conditions
- Coronavirus Infection
- Keywords
- Novel Coronavirus Infection, Probiotics, Lactobacillus, Bifidobacterium, Clinical outcomes, C.difficile, Diarrhea, Liver
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- I.M. Sechenov First Moscow State Medical UniversityUniversity, hospital or other
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 10 Mar 2021 (actual)
- Study completion
- 10 Apr 2021 (actual)
- First posted
- 22 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The treatment of the new coronavirus infection (COVID-19) and COVID-19-associated diarrhoea and liver injury remains challenging. Optimizing treatment approaches for COVID-19 remains an issue. It is assumed, that changes in composition of intestinal microbiota is closely related to a change in the regulation of the immune response in the lungs in patients with COVID-19. These gut microbiota changes in combination with antibiotic prescription during the treatment increase the risk of antibiotic-associated diarrhea and C. difficile infection as well as worse clinical outcomes in these patients. Probiotics are useful for restoring the human gut microbiome and increasing anti-inflammatory response also. Despite the variety of uses of probiotics, there is still insufficient data on the clinical efficacy of including probiotics in the treatment of patients with COVID-19 infection.
Detailed description
A randomized controlled open-label study approved by the local ethical committee. The study included patients with COVID-19 admitted to the T.M. Tareev Clinic of Internal Diseases of I.M. Sechenov First Moscow State Medical University in whom the disease was confirmed using polymerase chain reaction on nasopharyngeal and oropharyngeal swabs to detect severe acute respiratory syndrome-related coronavirus 2 (SARS-COV-2). The study was conducted from December 2020 to March 2021 and included participants in the age range from 18 to 75 years.
The exclusion criteria were age over 75 years or under 18 years, consumption of probiotics for 3 months prior to admission, history of intolerance to probiotics or their components, refusal to participate and sign informed consent, pregnancy or breastfeeding, cancer or mental illness, and severe renal (glomerular filtration rate less than 50 mL/min) or hepatic (equivalent to cirrhosis class B or C on the Child-Pugh scale) dysfunction at the time of admission.
Patients who prematurely discontinued the consumption of probiotics for reasons not related to the development of side effects were excluded from the study.
The patients were randomised to the probiotics group (PRO group) or the control group (CON group). Patients in the PRO group received probiotics containing ~109 colony forming units (CFU) of Lactobacillus rhamnosus PDV 1705, ~109 CFU of Bifidobacterium bifidum PDV 0903, ~109 CFU of B. longum subsp. infantis PDV 1911, and ~109 CFU of B. longum PDV 2301 three times a day during the hospital stay but for no more than 14 days (PDV is the commercial letter designation of the bacterial strains). The end point of the trial was day 14 of hospitalisation or the day of the patient's discharge or death, whichever occurred earlier.
The control group consisted of patients who did not receive probiotics. Patients in both the groups also received dexamethasone and antiviral (favipiravir and/or riamilovir), antibacterial, anticoagulant (enoxaparin in most cases; rivaroxaban and dabigatran were used much less frequently), and anticytokine (tocilizumab or/and olokizumab) drugs according to indications and contraindications.
Death from any cause was considered the primary outcome. Duration of hospitalisation, total duration of the disease, incidence of admission to intensive care unit, need for oxygen support or mechanical ventilation, and changes in the values of key biomarkers were considered the main secondary outcomes. The duration of diarrhoea [loose or watery stools or an increase in the frequency of bowel movements (more than three times per day)] and incidence of hospital-acquired diarrhoea as well as the progression of pre-existing liver injury and onset of liver injury were considered additional secondary outcomes. Liver injury was determined through the presence of abnormalities in any of the main liver test findings (serum alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, and albumin levels).
The volume of the affected lungs was measured using chest computed tomography (CT); it included the sum of ground glass and consolidation volumes.
Results are presented as the median [interquartile range]. The groups were compared using Mann-Whitney test for continuous data and chi-square test for categorical data. Wilcoxon test was used to assess the changes in continuous biomarker values. Mortality was assessed using the Kaplan-Meier estimator and Cox's test. A p value ≤0.05 was considered the criterion for significance. Statistical calculations were performed using "Statistica 10" soft (TIBCO Software inc, Palo Alto, CA)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics group (PRO) | Experimental | Other: Probiotics99 patients with COVID-19 infection who have been supplemented with a Lactobacillus and Bifidobacterium containing probiotic in addition to standard regimen (oxygen support, antiviral, antibacterial, anticoagulant, anticytokine (tocilizumab and olokizumab) drugs and dexamethasone treatment according to indications and contraindications) |
| Control group (CON) | No intervention | –101 patients with COVID-19 infection who have been treated with standard regimen only (oxygen support, antiviral, antibacterial, anticoagulant, anticytokine (tocilizumab and olokizumab) drugs and dexamethasone treatment according to indications and contraindications) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- patients with COVID-19 infection confirmed by polymerase chain reaction of nasopharyngeal and oropharyngeal swabs to the causative agent of this infection
- age from 18 to 75 years old from December 2020 to April 2021
Key exclusion criteria (11 listed)
- the patient's decision to withdraw from the study
- refusing to take the probiotic for a reason not related to the development of side effects.
- age over 75 years old or under 18 years old,
- taking probiotics for 3 months prior to admission
- history of intolerance to probiotics or their components
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbioticsProbiotics (10^9 CFU of each strain: Lactobacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911 and Bifidobacterium longum PDV 2301) 3 times per day in addition to standard treatment regimen for 2 weeks | Other | Probiotics group (PRO) |
Primary outcome
Mortality
Time frame: During hospitalization (Since the first day of hospitalization to the day of the patient's discharge)
The number of died patients during hospitalization
24 secondary outcomes
Duration of hospitalization
Time frame: Since the first day of hospitalization to the day of the patient's discharge
Total duration of the disease
Time frame: Since the first day of hospitalization to the day of the patient's discharge
Incidence of admission to intensive care unit
Time frame: at the 14th day of hospitalization or at the day of the patient's discharge
Need for non-invasive ventilation
Time frame: at the 14th day of hospitalization or at the day of the patient's discharge
Days of non-invasive ventilation
Time frame: at the 14th day of hospitalization or at the day of the patient's discharge
Need for invasive ventilation
Time frame: at the 14th day of hospitalization or at the day of the patient's discharge
Changes in the values of C-reactive protein level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of white blood cells in blood test
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of neutrophils in blood test
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of lymphocytes
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the counts of platelets
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of erythrocyte sedimentation rate in in blood test
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of creatinine level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of alanine aminotransferase (ALT) level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of aspartate aminotransferase level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of albumen level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of total bilirubin level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of lactate dehydrogenase level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of ferritin level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of fibrinogen level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Changes in the values of potassium level in serum
Time frame: at the first and at the 14th day of hospitalization (or at the first day and at day of the patient's discharge)
Incidence of diarrhoea
Time frame: at 14th day of hospitalization (or at the day of the patient's discharge)
The duration of diarrhoea
Time frame: at 14th day of hospitalization (or at the day of the patient's discharge)
The maximum volume of the affected lungs
Time frame: at 14th day of hospitalization (or at the day of the patient's discharge)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2022.
- Background: PubMed 32498503Madabhavi I, Sarkar M, Kadakol N. COVID-19: a review. Monaldi Arch Chest Dis. 2020 May 14;90(2). doi: 10.4081/monaldi.2020.1298.
- Background: PubMed 32896291Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatullin AI, Shcheblyakov DV, Dzharullaeva AS, Grousova DM, Erokhova AS, Kovyrshina AV, Botikov AG, Izhaeva FM, Popova O, Ozharovskaya TA, Esmagambetov IB, Favorskaya IA, Zrelkin DI, Voronina DV, Shcherbinin DN, Semikhin AS, Simakova YV, Tokarskaya EA, Lubenets NL, Egorova DA, Shmarov MM, Nikitenko NA, Morozova LF, Smolyarchuk EA, Kryukov EV, Babira VF, Borisevich SV, Naroditsky BS, Gintsburg AL. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020 Sep 26;396(10255):887-897. doi: 10.1016/S0140-6736(20)31866-3. Epub 2020 Sep 4.
- Background: PubMed 32753138Tariq R, Saha S, Furqan F, Hassett L, Pardi D, Khanna S. Prevalence and Mortality of COVID-19 Patients With Gastrointestinal Symptoms: A Systematic Review and Meta-analysis. Mayo Clin Proc. 2020 Aug;95(8):1632-1648. doi: 10.1016/j.mayocp.2020.06.003. Epub 2020 Jun 10.
- Background: PubMed 32749643Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, Khare S, Srivastava A. Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis. Indian J Gastroenterol. 2020 Jun;39(3):268-284. doi: 10.1007/s12664-020-01058-3. Epub 2020 Aug 4.
- Background: PubMed 32624655Rokkas T. Gastrointestinal involvement in COVID-19: a systematic review and meta-analysis. Ann Gastroenterol. 2020 Jul-Aug;33(4):355-365. doi: 10.20524/aog.2020.0506. Epub 2020 Jun 6.
- Background: PubMed 32681674Zarifian A, Zamiri Bidary M, Arekhi S, Rafiee M, Gholamalizadeh H, Amiriani A, Ghaderi MS, Khadem-Rezaiyan M, Amini M, Ganji A. Gastrointestinal and hepatic abnormalities in patients with confirmed COVID-19: A systematic review and meta-analysis. J Med Virol. 2021 Jan;93(1):336-350. doi: 10.1002/jmv.26314. Epub 2020 Jul 27.
- Background: PubMed 32457035Suresh Kumar VC, Mukherjee S, Harne PS, Subedi A, Ganapathy MK, Patthipati VS, Sapkota B. Novelty in the gut: a systematic review and meta-analysis of the gastrointestinal manifestations of COVID-19. BMJ Open Gastroenterol. 2020 May;7(1):e000417. doi: 10.1136/bmjgast-2020-000417.
- Background: PubMed 32407808Sultan S, Altayar O, Siddique SM, Davitkov P, Feuerstein JD, Lim JK, Falck-Ytter Y, El-Serag HB; AGA Institute. Electronic address: ewilson@gastro.org. AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19. Gastroenterology. 2020 Jul;159(1):320-334.e27. doi: 10.1053/j.gastro.2020.05.001. Epub 2020 May 11.
- Background: PubMed 32418852Wang H, Qiu P, Liu J, Wang F, Zhao Q. The liver injury and gastrointestinal symptoms in patients with Coronavirus Disease 19: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2020 Oct;44(5):653-661. doi: 10.1016/j.clinre.2020.04.012. Epub 2020 May 12.
- Background: PubMed 32405603Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, Shen J, Zhu LR, Chen Y, Iacucci M, Ng SC, Ghosh S, Chen MH. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020 Jul;5(7):667-678. doi: 10.1016/S2468-1253(20)30126-6. Epub 2020 May 12.
- Background: PubMed 32787470Bottari B, Castellone V, Neviani E. Probiotics and Covid-19. Int J Food Sci Nutr. 2021 May;72(3):293-299. doi: 10.1080/09637486.2020.1807475. Epub 2020 Aug 12.
- Background: PubMed 32085846Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.
- Individual participant dataSharing planned: No. The provision of data is prohibited by Local Ethical Committee and is possible upon receipt of an official request addressed to the principal investigator
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotics in people with Coronavirus Infection, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: During hospitalization (Since the first day of hospitalization to the day of the patient's discharge)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04854941, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2022.