Inulin for Infections in the Intensive Care Unit

NCT03865706 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AAAS2576PR181960
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Microbiome; Antibiotic resistance; Intensive care unit; Sepsis; Nutrition; Pathogen colonization

Outcome Measures

Primary Outcomes (1)

• Within-individual Change in SCFA Producer Level

  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.

  Baseline and Day 3

Secondary Outcomes (2)

• 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

Other Outcomes (4)

• Fecal Short Chain Fatty Acid (SCFA) Levels

  Days 3 and 7

• ICU Length of Stay (LOS)

  through ICU Day 30

• Multidrug Resistant (MDR) Infections

  through 30 days

Study Arms (3)

Inulin 32 g/day

EXPERIMENTAL

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

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

Inulin 16 g/day

EXPERIMENTAL

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

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

Placebo

PLACEBO COMPARATOR

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

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

Interventions

Inulin Oral Suspension DRUG

Inulin powder, derived from chicory root and re-suspended in 250cc water Dosage will be either 8g twice a day or 16g twice a day - dissolved in 250cc sterile water, given oral or via enteric tube

Also known as: Inulin

Inulin 16 g/day; Inulin 32 g/day

Placebo Oral Suspension DRUG

250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor

Also known as: Placebo

Placebo

Broad-spectrum antibiotics DRUG

Standard of care treatment for infections

Also known as: Antibiotics

Inulin 16 g/day; Inulin 32 g/day; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10023, United States

Location

Related Publications (2)

• Park H, Abrams JA, Uhlemann AC, Freedberg DE. Gut Colonization With Vancomycin-Resistant Enterococcus Shapes the Gut Microbiome in the Intensive Care Unit. J Infect Dis. 2025 Sep 15;232(3):669-678. doi: 10.1093/infdis/jiaf194.

  PMID: 40237647 DERIVED

• Park H, Lynch E, Tillman A, Lewis K, Jin Z, Uhlemann AC, Abrams JA, Freedberg DE. A phase 2 randomized, placebo-controlled trial of inulin for the prevention of gut pathogen colonization and infection among patients admitted to the intensive care unit for sepsis. Crit Care. 2025 Jan 13;29(1):21. doi: 10.1186/s13054-024-05232-3.

  PMID: 39806400 DERIVED

MeSH Terms

Conditions

Cross Infection; Nutrition Disorders; Critical Illness; Sepsis

Interventions

Inulin; Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Infections; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Daniel E. Freedberg, MD, MS
• Organization: Columbia University

def2004@cumc.columbia.edu

857-998-9370

Study Officials

• Daniel E Freedberg, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind, randomized
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine and Epidemiology

Model Details: placebo-controlled trial with 1:1:1 enrollment into three arms: inulin 32 g/day, inulin 16 g/day, and placebo

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 7, 2019
• Study Start: October 14, 2019
• Primary Completion: November 21, 2023
• Study Completion: July 23, 2024
• Last Updated: June 19, 2025
• Results First Posted: December 17, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)