Randomized Trial to Study the Effect of Rifaximin on Gut Microbiome Diversity Post Allogeneic Stem Cell Transplant in Acute Leukemia.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 166
- 试验地点
- 1
- 主要终点
- Impact of rifaximin on gut microbial diversity.
研究概览
简要总结
- Goal: This study is a randomized phase II interventional study. The purpose of this study is to see if addition of oral rifaximin tablets during allogeneic stem cell transplant can improve the quality of gut microbiome and reduce chances of death, infections and graft versus host disease (GVHD) post-transplant.
- The study objectives are as follows:
- Primary Objective: To determine the impact of rifaximin on gut microbial diversity and compare it with controls.
- Secondary Objectives: a. To determine non-relapse mortality at 1-year post transplant in patients who receive peri-transplant transplant rifaximin and compare it with controls.
- b. To compare the incidence of severe GVHD in patients who receive peri-transplant rifaximin with the controls.
- c. To determine impact of gut decontamination with rifaximin on incidence of MDR sepsis and usage of higher antibiotics (e.g. Carbapenems, colistin, tigecycline, ceftazidime avibactum and ceftriaxone-sulbactam EDTA) in first 6 months post BMT.
- d. To determine the impact of rifaximin induced gut manipulation on immune reconstitution, T cell repertoire post-transplant and cytokine profile.
- Exploratory objective: To use single cell transcriptomics (SCT) to identify immune cell profile in gut biopsies post allogeneic stem cell transplant whenever biopsy is done, to correlate the impact of microbiome on gut immunity.
- Intervention: Tab Rifaximin 200 mg will be given orally twice daily from day -8 to day +60 of allogeneic stem cell transplant in acute leukemia patients. This will be in addition to standard of care post-transplant treatment.
- Comparator Agent: Standard of care treatment including standard anti GVHD measures, antibiotic support and transfusions as needed.
详细描述
The gut microbiome plays a significant role in modulating the immune re-constitution post allogeneic stem cell transplant (ASCT). Low gut microbial diversity has been consistently associated with poor outcomes of transplant including increased incidence of acute graft versus host disease (aGVHD), post-transplant bacterial sepsis and non-relapse mortality (NRM). However, the exact mechanism by which gut microbiome influences local as well as systemic immunity is not completely known, and is thought to be due to the impact of microbial metabolites on intestinal epithelial cells and host antigen-presenting cells. Understanding these mechanisms and modulating the microbiome may be crucial to improving transplant outcomes. Rifaximin is a locally acting antibiotic that has been approved for manipulating the gut microbiome in hepatic failure. It is unique because of its ability to clear pathogenic bacteria, while preserving the anaerobic commensals. It can potentially modify the gut microbiome to increase the alpha diversity and this may help reduce aGVHD, infectious complications, and mortality post-transplant. High incidence of multidrug resistant sepsis and frequent use of broad spectrum antibiotics in India, would result in higher rates of dysbiotic gut- making microbiome manipulation to improve transplant outcomes more relevant in our country. We are proposing a randomized controlled trial to understand the benefits of modulating the gut microbiome in patients of ASCT while investigating the local and global immune repertoire using single cell sequencing and multicolour flow cytometry.
Study design: Single center, open-labeled, phase II study, randomized controlled trial.
Primary Objective: To determine the impact of rifaximin on gut microbial alpha diversity and compare it with controls.
Secondary Objectives:
To determine impact of rifaximin on 1 year non relapse mortality post-transplant, incidence of grade III/IV aGVHD, incidence of MDR sepsis, patterns of immune cell reconstitution, and cytokine profile post-transplant.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults with acute leukemia undergoing allogeneic stem cell transplant.
- •ECOG performance status 0, 1 or
- •Adequate Liver function
排除标准
- •Known hypersensitivity to rifaximin or other rifampicin antimicrobial agents
- •Current or past history of inflammatory bowel disease
- •History of major bowel resection or presence of colostomy.
- •Ongoing Verapamil, ketoconazole or itraconazole.
研究组 & 干预措施
Rifaxmin +aHSCT
drug rifaximin 200 mg tablet form orally twice daily (with or without food) from day-8 of transplant to day + 60 of transplant
干预措施: Rifaximin 200Mg Tab (Drug)
aHSCT alone
control arm will underwent allogenic hematopoietic stem cell transplantation procedure as per standard of care
干预措施: allogenic hematopoietic stem cell transplantation (Procedure)
结局指标
主要结局
Impact of rifaximin on gut microbial diversity.
时间窗: 14 days post transplant
Gut microbial diversity as measured by inverse Simpson index (ISI) on stool samples on day 14 post transplant in Rifaximin arm and in controls.
次要结局
- Impact of rifaximin induced gut manipulation on immune reconstitution(1 year post transplant)
- Non relapse mortality(1 year post transplant)
- Incidence of severe (grade III/IV) acute graft versus host disease(1 year post transplant)
- Impact of gut decontamination with rifaximin on incidence of multidrug resistant sepsis post transplant.(6 months post transplant)