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NCT03865706

Inulin for Infections in the Intensive Care Unit

Completed Phase 2 Results posted Last updated 19 June 2025
What this trial tests

Phase 2 trial testing Inulin Oral Suspension in Antibiotic Resistant Infection in 94 participants. Completed in 23 July 2024.

Timeline
14 October 2019
Primary endpoint
21 November 2023
23 July 2024

Quick facts

Lead sponsorColumbia University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment94
Start date14 October 2019
Primary completion21 November 2023
Estimated completion23 July 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Columbia University

Who can join

18 and older, any sex, with Antibiotic Resistant Infection or Nosocomial Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Within-individual Change in SCFA Producer Level Primary · 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.

GroupValue95% CI
Placebo-0.0-7.9 – 7.4
Inulin 16 g/Day-1.8-8.9 – 3.7
Inulin 32 g/Day1.1-12 – 11
Multidrug Resistant Organism (MDRO)-Gram Negative Bacteria (GNB) Colonization Status Secondary · Day 0 and at last sample collected, up to Day 30

Proportion of patients who are MDRO-GNB colonized within each treatment group, with MDRO-GNB colonization status classified categorically based on the presence or absence of methicillin-resistant Staphylococcus aureus (MRSA) or Gram negative bacteria (GNB) with third-generation cephalosporins non-susceptibility

Day 0
GroupValue95% CI
Placebo6
Inulin 16 g/Day4
Inulin 32 g/Day3
Last Sample Collected, Up to Day 30
GroupValue95% CI
Placebo3
Inulin 16 g/Day4
Inulin 32 g/Day3
Fecal Short Chain Fatty Acid (SCFA) Levels Secondary · Days 3 and 7

The SCFAs butyrate, acetate, and propionate will be measured from whole stools on a 6490 triple quadrupole mass spectrometer and compared between intervention groups using the first stool sample produced after the Day 3 assessment. Patients who fail to produce a stool from Day 3 to 7 will be excluded from this analysis.

Day 3
GroupValue95% CI
Placebo00 – 0.18
Inulin 16 g/Day0.110 – 0.66
Inulin 32 g/Day00 – 0.46
Day 7
GroupValue95% CI
Placebo00 – 0.06
Inulin 16 g/Day0.290 – 0.63
Inulin 32 g/Day00 – 0.19
ICU Length of Stay (LOS) Secondary · through ICU Day 30

compared between groups, after adjusting for death as a competing risk

GroupValue95% CI
Placebo9.56 – 20
Inulin 16 g/Day10.56 – 23
Inulin 32 g/Day96 – 17
Multidrug Resistant (MDR) Infections Secondary · through 30 days

proportion of patients with culture-proven infections within each treatment group, with culture-proven infections defined as those that have (1) an organism meeting MDRO criteria from a clinical culture, (2) signs and symptoms of infection by Centers for Disease Control (CDC)/National Health and Safety Network (NHSN) guideline definitions, and (3) receive appropriate antibiotics from the treating team

GroupValue95% CI
Placebo15
Inulin 16 g/Day9
Inulin 32 g/Day12
Mortality Secondary · Day 90

Death data will be extracted from the hospital electronic medical record (EMR) which immediately captures in-hospital death and receives monthly mortality updates from the National social security death index.

GroupValue95% CI
Placebo7
Inulin 16 g/Day7
Inulin 32 g/Day9
Vancomycin-resistant Enterococcus (VRE) Colonization Status Secondary · Day 0 and at last sample collected, up to Day 30

Proportion of patients who are VRE colonized within each treatment group, with VRE colonization status classified categorically based on the presence or absence of vancomycin-resistant Enterococcus (VRE)

Day 0
GroupValue95% CI
Placebo8
Inulin 16 g/Day6
Inulin 32 g/Day4
Last Sample Collected, Up to Day 30
GroupValue95% CI
Placebo11
Inulin 16 g/Day13
Inulin 32 g/Day6

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 90. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/30 (0%)
Deaths: 7/30
Inulin 16 g/Day
Serious: 0/30 (0%)
Deaths: 7/30
Inulin 32 g/Day
Serious: 0/30 (0%)
Deaths: 9/30
Other adverse events (4 terms — click to expand)

ReactionSystemPlaceboInulin 16 g/DayInulin 32 g/Day
DiarrheaGastrointestinal disorders
Culture Proven InfectionInfections and infestations
BloatingGastrointestinal disorders
VomitingGastrointestinal disorders

Data from ClinicalTrials.gov NCT03865706 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The Role of Probiotics, Prebiotics and Synbiotics in Combating Multidrug-Resistant Organisms.
    Newman AM, Arshad M. · · 2020 · cited 40× · PMID 32800382 · DOI 10.1016/j.clinthera.2020.06.011
  2. Decreased Gut Microbiome Tryptophan Metabolism and Serotonergic Signaling in Patients With Persistent Mental Health and Gastrointestinal Symptoms After COVID-19.
    Blackett JW, Sun Y, Purpura L, Margolis KG, et al · · 2022 · cited 23× · PMID 36049050 · DOI 10.14309/ctg.0000000000000524
  3. Impact of Fiber-Based Enteral Nutrition on the Gut Microbiome of ICU Patients Receiving Broad-Spectrum Antibiotics: A Randomized Pilot Trial.
    Freedberg DE, Messina M, Lynch E, Tess M, et al · · 2020 · cited 17× · PMID 32695998 · DOI 10.1097/cce.0000000000000135
  4. Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms.
    Feehan A, Garcia-Diaz J. · · 2020 · cited 14× · PMID 31991615 · DOI 10.3390/microorganisms8020166
  5. 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.
    Park H, Lynch E, Tillman A, Lewis K, et al · · 2025 · cited 8× · PMID 39806400 · DOI 10.1186/s13054-024-05232-3
  6. Are There Bad ICU Rooms? Temporal Relationship between Patient and ICU Room Microbiome, and Influence on Vancomycin-Resistant <i>Enterococcus</i> Colonization.
    Freedberg DE, Richardson M, Nattakom M, Cheung J, et al · · 2022 · cited 5× · PMID 35107335 · DOI 10.1128/msphere.01007-21
  7. Effect of dietary fibre on the gastrointestinal microbiota during critical illness: A scoping review.
    Ghosh AN, Walsh CJ, Maiden MJ, Stinear TP, et al · · 2025 · cited 2× · PMID 40060735 · DOI 10.5492/wjccm.v14.i1.98241
  8. Gut Colonization With Vancomycin-Resistant Enterococcus Shapes the Gut Microbiome in the Intensive Care Unit.
    Park H, Abrams JA, Uhlemann AC, Freedberg DE. · · 2025 · cited 1× · PMID 40237647 · DOI 10.1093/infdis/jiaf194

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