Effect of Oral Probiotics Streptococcus Salivarius K12 and Lactobacillus Brevis CD2 on the Prevention of Secondary Bacterial Pneumonia in Patients With Severe COVID-19: a Phase II Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- Secondary bacterial pneumonia
研究概览
简要总结
Background and aims: Patients with severe Coronavirus Disease 2019 (COVID-19) are prone to secondary bacterial pneumonia. The use of probiotics against oral pathogens might prevent lung colonization and progression to bacterial pneumonia. This study aimed to assess the effect of Streptococcus salivarius K12 combined with Lactobacillus brevis CD2 in preventing secondary bacterial pneumonia in patients with severe COVID-19. Methods: This randomized placebo-controlled phase 2 trial involved 70 patients with severe COVID-19 admitted to the intensive care unit (ICU). Patients were randomly assigned to a 7-day course of oral gel containing Streptococcus salivarius K12 2 billion colony-forming units (CFU) and Lactobacillus brevis CD2 4 billion CFU every 8 hours or placebo, starting in the first ICU day. The primary outcome was bacterial pneumonia, established according to clinical, laboratory, radiological, and microbiological findings, whereas secondary outcomes were ICU stay in days and hospital mortality.
详细描述
Design This was a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Setting All participants were studied after admission on ICU at the Clinics Hospital of Passo Fundo (HCPF). This institution is a regional reference for the treatment of patients with COVID-19, with ICU specialized for this condition, serving an estimated population over 500,000 inhabitants.
Participants Adult patients with suspected or confirmed diagnosis of COVID-19 who presented to the HCPF with severe acute respiratory syndrome, requiring ICU admission, were invited to participate. This project followed the rules of the Helsinki Declaration and was carried out after approval by the Ethics Committee of the HCPF and the Research Ethics Committee of the UPF/CONEP. Patients were included after signing the consent form, by the patient or his/her guardian.
ICU management The patients followed the clinical routine practiced in the HCPF ICU. They received measures of non-invasive and invasive ventilatory support, hemodynamic, nutritional, among others, in addition to specific treatment for COVID-19 in severe cases, using drugs at the discretion of the hospital protocol, in addition to broad-spectrum antibiotic therapy in suspected superimposed bacterial infection. Monitoring of the pulmonary condition was performed with routine tests including laboratory, imaging, microbiology.
Probiotic and placebo Patients were treated with a gel containing Streptococcus salivarius K12 (2 billion live bacilli) and Lactobacillus brevis CD2 (4 billion live bacilli) or a placebo. This amount of probiotics (and placebo) was prepared in a sachet containing one gram of gel, by a local compounding pharmacy (NATUPHARMA, probiotics marketed by FRAGON, Netherlands). These probiotics are exempt from registration with The Brazilian Health Regulatory Agency (ANVISA). Each patient received 1 gram of oral gel every 8 hours for 7 days, applied by the researcher. It should be noted that all researchers followed the current care protocols for the prevention of contamination by the new coronavirus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Oral probiotics and placebo were physically identical and were revealed after statistical analysis
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients hospitalized in the ICU with severe acute respiratory syndrome
- •progressive deterioration of the ventilatory status in the first 48 hours in the ICU, which may require mechanical ventilation within this period;
- •confirmed diagnosis of COVID-19 within 3 days of ICU admission;
- •acceptance to participate.
排除标准
- •relevant immunodeficiency (decompensated HIV, aggressive immunosuppression, terminal cancer)
- •decompensated systemic disease before the onset of COVID-19.
结局指标
主要结局
Secondary bacterial pneumonia
时间窗: From date of randomization until the date of first documented secondary bacterial pneumonia or date of death from any cause, whichever came first, assessed up to 90 days.
In patients with severe COVID-19 managed in ICU, the occurrence of symptoms and signs of secondary bacterial pneumonia
次要结局
- ICU stay(up to 90 days)
- hospital mortality(up to 90 days)
研究者
Fernando Fornari
Professor
Universidade de Passo Fundo