Inulin for Infections in the Intensive Care Unit

Phase 2

Completed

Conditions: Sepsis
Antibiotic Resistant Infection
Nutrition Disorders
Critical Illness
Nosocomial Infection
Pathogen Transmission

Interventions: Drug: Inulin Oral Suspension
Drug: Placebo Oral Suspension
Drug: Broad-spectrum antibiotics

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.

Recruitment & Eligibility

Inclusion Criteria

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

Exclusion Criteria

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)

Arm && Interventions

Group	Intervention	Description
Inulin 32 g/day	Inulin Oral Suspension	Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.
Inulin 32 g/day	Broad-spectrum antibiotics	Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.
Inulin 16 g/day	Inulin Oral Suspension	Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.
Inulin 16 g/day	Broad-spectrum antibiotics	Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.
Placebo	Placebo Oral Suspension	Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.
Placebo	Broad-spectrum antibiotics	Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.

Primary Outcome Measures

Name	Time	Method
Within-individual Change in SCFA Producer Level	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.

Secondary Outcome Measures

Name	Time	Method
Multidrug Resistant Organism (MDRO) Colonization Status	Day 3	proportion of patients who are MDRO colonized within each treatment group, with MDRO colonization status classified categorically based on the presence or absence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), or Gram negative bacteria with third-generation cephalosporins non-susceptibility

Locations (1): Columbia University Medical Center
🇺🇸
New York, New York, United States