Prevention of Febrile Neutropenia in Pediatric Cancer Patients by Lactobacillus Rhamnosus GG and Bifidobacterium Animalis Subspecies. Lactis BB-12 in Combination With Inulin and Oligofructose
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Reduction in the incidence of febrile neutropenia episodes
研究概览
简要总结
Febrile neutropenia (FN) is a major life-threatening treatment complication in cancer patients undergoing intensive chemotherapy. Endogenous flora is considered to be one of the main sources of infections during neutropenia. Competitive inhibition of gut mucosal colonization by pathogenic microorganisms using synbiotics could represent one of the potential options for its prevention. Synbiotics represent combination of two components: probiotics and prebiotics. Probiotics are live microorganisms, which in form of drugs or food supplements administered at a sufficient dose help to maintain health beneficial microbial balance in the digestive tract of a human or other host. Prebiotics are food ingredients nondigestible for our digestive enzymes, but can be fermented by bacteria in our bowel and this way selectively stimulate growth or activity of specific saccharolytic bacterial strains. These changes in composition of our microflora may bring benefits on host well-being and health. Based on the results of human and animal studies, probiotics probably can not only decrease the level of gut colonisation with pathogenic bacteria, but may also lead to reduction in the duration of neutropenia, accelerate the restitution of the intestinal mucosa and boost immunity. Despite a significant number of studies on probiotics still only little evidence of their safety especially in immunocompromised patients is available.
To help find new options for increasing quality of healthcare for children cancer patients and also to evaluate safety of this new approach investigators designed double-blinded placebo controled multicenter study aimed to decrease the number of febrile episodes using prevention with synbiotic.
详细描述
Febrile neutropenia (FN) is a major complication in cancer patients undergoing intensive chemotherapy. Endogenous flora is considered to be one of the main sources of infections in neutropenic patients. The first step in infection process is colonization of the intestine by pathogenic bacteria with their subsequent translocation through the intestinal mucosa and systemic dissemination.
The alterations of the intestinal flora occurs due to chemotherapy and also due to the use of broad spectrum antibiotics, which suppresses anaerobic growth of the normal gut flora leading to a damage of colonization resistance. Competitive inhibition of gut mucosal colonization by pathogenic micro-organisms using synbiotics could represent one of the potential options for the prevention of febrile neutropenia in cancer patients. Compared with the existing selective bowel decontamination with quinolones and/or trimethoprim-sulfamethoxazole, investigators may expect also reduction of the incidence of fungal and Gram-positive infections due to changes in the intestinal microflora. Based on the results of animal studies, probiotics could probably also lead to a reduction in the duration of neutropenia and boost immunity.
Synbiotics represent combination of two components: probiotics and prebiotics. Probiotics are live microorganisms, which in form of drugs or food supplements administered at a sufficient dose help to maintain health beneficial microbial balance in the digestive tract of a human or other host. Prebiotics are food ingredients nondigestible for our digestive enzymes, but can be fermented by bacteria in our bowel and this way selectively stimulate growth or activity of specific saccharolytic bacterial strains.
Lactic acid bacteria are currently widely used in prevention and treatment of certain infectious diseases. They stimulate the immune system, compete for substrate with pathogenic bacteria, produce bacteriocins, competitively inhibit bacterial adhesion sites, increase the transepithelial resistance and bind some mutagens.
Current evidence supporting probiotic use as adjunctive therapy to anticancer treatment is limited, especially in cancer patients treated with chemotherapy. Some of the reports support their beneficial effects on certain aspects of toxicity related to chemotherapy and radiation therapy; however, large properly designed clinical trials are needed to assess their real position as a part of anticancer treatment.
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)
入排标准
- 年龄范围
- 6 Months 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •newly diagnosed cancer disease prior to initiation of chemotherapy
- •Eastern Cooperative Oncology Group performance status = 0-1
- •informed consent has to be given by patients, respectively their legal representatives
- •age between 6 months to 19 years
- •must be afebrile and no other signs of infection at least 24 hours before starting of prophylaxis
- •must not taking other probiotic or prebiotic preparations or discontinued their use more than 14 days ago
排除标准
- •impossibility of oral intake
- •receiving any other type of experimental prophylaxis
- •estimated survival time of less than 4 weeks
- •allogeneic or autologous bone marrow transplantation
- •inflammatory bowel disease
结局指标
主要结局
Reduction in the incidence of febrile neutropenia episodes
时间窗: 3 months
Febrile neutropenia is defined as an oral temperature \>38.3°C or two consecutive readings of \>38.0°C sustained for more than 1 hour and an absolute neutrophil count \<0.5 × 109/l, or expected to fall below 0.5 × 109/l in the next 48-hour period
次要结局
- Time period to first febrile episode(3 months)
- Reduction in the number of septic complications requiring intensive care(3 months)
- Reduction in the incidence of diarrhea and enterocolitis episodes related to chemotherapy(3 months)
- Reduction of the total duration of febrile neutropenia(3 months)
- Reduction in the number of infectious episodes outside the period of neutropenia(3 months)
- Safety evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(3 months)