Efficacy of Probiotics in the Treatment of Hospitalised Patients With Novel Coronavirus Infection

NCT04854941 | Completed DMC

• 1 other identifier: PROCOV-19-2020
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Coronavirus Infection

Keywords

Novel Coronavirus Infection; Probiotics; Lactobacillus; Bifidobacterium; Clinical outcomes; C.difficile; Diarrhea; Liver; mortality

Outcome Measures

Primary Outcomes (1)

• Mortality

  The number of died patients during hospitalization

  During hospitalization (Since the first day of hospitalization to the day of the patient's discharge)

Secondary Outcomes (24)

• Duration of hospitalization

  Since the first day of hospitalization to the day of the patient's discharge

• Total duration of the disease

  Since the first day of hospitalization to the day of the patient's discharge

• Incidence of admission to intensive care unit

  at the 14th day of hospitalization or at the day of the patient's discharge

• Need for non-invasive ventilation

  at the 14th day of hospitalization or at the day of the patient's discharge

• Days of non-invasive ventilation

  at the 14th day of hospitalization or at the day of the patient's discharge

Study Arms (2)

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)

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)

Interventions

Probiotics OTHER

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

Probiotics group (PRO)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• I.M. Sechenov First Moscow State Medical University: lead

Study Sites (1)

I.M. Sechenov First Moscow State Medical University

Moscow, 119991, Russia

Location

Related Publications (15)

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• Logunov 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.

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• Kumar 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.

  PMID: 32749643 BACKGROUND

• Rokkas 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.

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• Zarifian 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.

  PMID: 32681674 BACKGROUND

• Suresh 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.

  PMID: 32457035 BACKGROUND

• Sultan 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.

  PMID: 32407808 BACKGROUND

• Wang 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.

  PMID: 32418852 BACKGROUND

• Mao 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.

  PMID: 32405603 BACKGROUND

• Bottari 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.

  PMID: 32787470 BACKGROUND

• Xu 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.

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• Spigaglia 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.

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• d'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.

  PMID: 32733907 BACKGROUND

• Ivashkin 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.

  PMID: 34643888 RESULT

MeSH Terms

Conditions

Coronavirus Infections; Diarrhea

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 22, 2021
• Study Start: December 10, 2020
• Primary Completion: March 10, 2021
• Study Completion: April 10, 2021
• Last Updated: January 28, 2022

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)