Prebiotic Inulin to Limit Antimicrobial-Resistant Infections During Critical Illness: A Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Within-individual Change in SCFA Producer Level
研究概览
简要总结
Normal gut bacteria prevent colonization and subsequent infection with MDR organisms (MDROs) through competition for resources and other mechanisms. During critical illness, this function of the microbiome is lost and there are no current treatments to restore it. Preliminary data indicates that the prebiotic fiber inulin is safe and may alter the gastrointestinal microbiome to improve gut barrier function, decrease colonization with MDROs, and reduce downstream risk for intensive care unit (ICU)-acquired MDR infections. However, the impact of inulin during critical illness is unknown. This double-blind, randomized clinical trial will test inulin for the prevention of antibiotic resistant infections in the ICU.
The trial's specific aims are to determine (1) the feasibility, tolerability, and safety of inulin in the intensive care unit; (2) the impact of inulin on gut colonization with antibiotic-resistant pathogens; and (2A/exploratory) the impact of inulin on ICU-acquired antibiotic-resistant infections.
详细描述
The proposed trial hypothesizes that inulin maintains short-chain fatty acid (SCFA)-producing colonic anaerobes and that these bacteria are protective against multi-drug resistant organism (MDRO) colonization and subsequent MDR infection. Inulin, a vegetable-derived non-digestible polysaccharide is well established as the key nutrient source for SCFA-producing bacteria. Previous human studies have shown that (1) inulin increases levels of SCFA producers and SCFAs and (2) that this increase correlates with improved colonic mucosal integrity and resistance to MDR pathogens. In animal studies, inulin improves survival after pathogen challenge or injection with lipopolysaccharide. The overall aim of this clinical trial is to determine whether inulin improves gut colonization resistance against antibiotic-resistant pathogens and therefore prevents antibiotic-resistant infections in the setting of critical illness. To accomplish this, 90 critically ill adults who are receiving broad-spectrum antibiotics will be blindly randomized 1:1:1 to receive placebo, inulin 8 g twice daily, or inulin 16 g twice daily for a minimum of 7 days, with bedside follow-up extending to 30 days or hospital discharge.
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
double-blind, randomized
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
- •Hospitalized in an eligible medical ICU
- •Age ≥ 18 years old at the time of hospitalization
- •With sepsis as defined by the Sepsis-3 (2016) consensus as a known or suspected infection with a sequential organ failure assessment (SOFA) score of ≥2 points above baseline
- •Received broad-spectrum antibiotics within the last 24 hours or ordered and pending administration
- •Able to complete enrollment within 4 hours of ICU admission for administration of the intervention within 6 hours of ICU admission
排除标准
- •Inability to receive oral or enteric fluids
- •Inulin allergy
- •Hyponatremia (serum sodium ≤128 mEq/L)
- •Immunosuppression, defined as history of solid organ transplant or as receipt of ablative chemotherapy, steroids at the equivalent of ≥5 mg/day prednisone, antimetabolites, anti-tumor necrosis factor (TNF) α agents, calcineurin inhibitors, or mycophenolate
- •Surgery involving the intestinal lumen within 30 days or known intestinal strictures
- •Do Not Resuscitate (DNR) or Do Not Intubate (DNI) status, or "no escalation of care" orders
- •Lack capacity for consent and no appropriate Legally Authorized Representative (LAR)
研究组 & 干预措施
Inulin 32 g/day
Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.
干预措施: Inulin Oral Suspension (Drug)
Inulin 32 g/day
Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.
干预措施: Broad-spectrum antibiotics (Drug)
Inulin 16 g/day
Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.
干预措施: Inulin Oral Suspension (Drug)
Inulin 16 g/day
Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.
干预措施: Broad-spectrum antibiotics (Drug)
Placebo
Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.
干预措施: Placebo Oral Suspension (Drug)
Placebo
Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.
干预措施: Broad-spectrum antibiotics (Drug)
结局指标
主要结局
Within-individual Change in SCFA Producer Level
时间窗: Baseline and Day 3
Relative abundance (i.e., proportion) of SCFA producing bacteria within each treatment group, will be assessed via 16S sequencing of rectal swabs. Modified intent-to-treat, comparing baseline vs Day 3 levels of SCFAs among those who receive one or more doses of the intervention and complete both assessments.
次要结局
- Multidrug Resistant Organism (MDRO)-Gram Negative Bacteria (GNB) Colonization Status(Day 0 and at last sample collected, up to Day 30)
- Vancomycin-resistant Enterococcus (VRE) Colonization Status(Day 0 and at last sample collected, up to Day 30)
研究者
Daniel Freedberg, MD
Assistant Professor of Medicine and Epidemiology
Columbia University