Clinical trial NCT03865706: Inulin for Infections in the Intensive Care Unit
Official title: Prebiotic Inulin to Limit Antimicrobial-Resistant Infections During Critical Illness: A Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Antibiotic Resistant Infection
Nosocomial Infection
Pathogen Transmission
Nutrition Disorders
Critical Illness
Sepsis
Keywords: Microbiome
Antibiotic resistance
Intensive care unit
Sepsis
Nutrition
Pathogen colonization
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2019-03-07
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-controlled trial with 1:1:1 enrollment into three arms: inulin 32 g/day, inulin 16 g/day, and placebo
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Hospitalized in an eligible medical ICU
2. Age ≥ 18 years old at the time of hospitalization
3. 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
4. Received broad-spectrum antibiotics within the last 24 hours or ordered and pending administration
5. Able to complete enrollment within 4 hours of ICU admission for administration of the intervention within 6 hours of ICU admission

Exclusion Criteria:

1. Inability to receive oral or enteric fluids
2. Inulin allergy
3. Hyponatremia (serum sodium ≤128 mEq/L)
4. 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
5. Surgery involving the intestinal lumen within 30 days or known intestinal strictures
6. Do Not Resuscitate (DNR) or Do Not Intubate (DNI) status, or "no escalation of care" orders
7. Lack capacity for consent and no appropriate Legally Authorized Representative (LAR)

Primary outcomes:
measure: Within-individual Change in SCFA Producer Level
timeFrame: Baseline and Day 3
Secondary outcomes:
measure: Multidrug Resistant Organism (MDRO) Colonization Status
timeFrame: Day 3
Other outcomes:
measure: Fecal Short Chain Fatty Acid (SCFA) Levels
timeFrame: outcomes focus on Day 3 and re-analyzed based on Day 7
measure: Nutritional Intake
timeFrame: through Day 3 and through Day 7
measure: ICU Length of Stay (LOS)
timeFrame: through ICU Day 30
measure: Multidrug Resistant (MDR) Infections
timeFrame: through 30 days
measure: Mortality
timeFrame: Day 90
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Daniel E Freedberg, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: