Inulin for Infections in the Intensive Care Unit

Columbia University

Status and phase: Completed; Phase 2

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

Treatments: Drug: Inulin Oral Suspension; Drug: Placebo Oral Suspension; Drug: Broad-spectrum antibiotics

Study type: Interventional

Funder types: Other

Identifiers

NCT03865706

PR181960 (Other Grant/Funding Number)

AAAS2576

Details and patient eligibility

About

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.

Full 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.

Enrollment: 94 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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94 participants in 3 patient groups, including a placebo group

Inulin 32 g/day

Experimental group

Description:

Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.

Treatment:

Drug: Broad-spectrum antibiotics

Drug: Inulin Oral Suspension

Inulin 16 g/day

Experimental group

Description:

Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.

Treatment:

Drug: Broad-spectrum antibiotics

Drug: Inulin Oral Suspension

Placebo

Placebo Comparator group

Description:

Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.

Treatment:

Drug: Broad-spectrum antibiotics

Drug: Placebo Oral Suspension