Efficacy of Probiotics (Lactobacillus Rhamnosus, Bifidobacterium Bifidum, Bifidobacterium Longum Subsp. Infantis and Bifidobacterium Longum) in the Treatment of Hospitalised Patients With Novel Coronavirus Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Mortality
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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)
结局指标
主要结局
Mortality
时间窗: During hospitalization (Since the first day of hospitalization to the day of the patient's discharge)
The number of died patients during hospitalization
次要结局
- 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)
- Need for invasive ventilation(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(at 14th day of hospitalization (or at the day of the patient's discharge))
- The duration of diarrhoea(at 14th day of hospitalization (or at the day of the patient's discharge))
- The maximum volume of the affected lungs(at 14th day of hospitalization (or at the day of the patient's discharge))