Antibiotic Resistant InfectionPhase 2NCT03865706
Inulin for Infections in the Intensive Care Unit
A Phase 2 study testing Inulin Oral Suspension and Broad-spectrum antibiotics in people with Antibiotic Resistant Infection and Nosocomial Infection, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibiotic Resistant Infection, Nosocomial Infection, Pathogen Transmission
- What is being tested?
- Inulin Oral Suspension and Broad-spectrum antibiotics
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2019to 23 Jul 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10023
About this study
Official title: Prebiotic Inulin to Limit Antimicrobial-Resistant Infections During Critical Illness: A Phase II Clinical Trial
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.
Read the 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.
- Conditions
- Antibiotic Resistant Infection, Nosocomial Infection, Pathogen Transmission, Nutrition Disorders, Critical Illness, Sepsis
- Being tested
- Inulin Oral Suspension, Placebo Oral Suspension, Broad-spectrum antibiotics
- Keywords
- Microbiome, Antibiotic resistance, Intensive care unit, Sepsis, Nutrition, Pathogen colonization
- Medical subject headings
- Cross Infection, Nutrition Disorders, Critical Illness, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inulin Oral SuspensionDrug
Also called Inulin
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
Placebo Oral SuspensionDrug
Also called Placebo
250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor
Broad-spectrum antibioticsDrug
Also called Antibiotics
Standard of care treatment for infections
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo Oral Suspension; Drug: Broad-spectrum antibiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Day 3
Secondary outcomes (2)
Multidrug Resistant Organism (MDRO)-Gram Negative Bacteria (GNB) Colonization Status
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
Measured: Day 0 and at last sample collected, up to Day 30
Vancomycin-resistant Enterococcus (VRE) Colonization Status
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)
Measured: Day 0 and at last sample collected, up to Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start14 Oct 2019
- Primary completion21 Nov 2023
- Study completion23 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Antibiotic Resistant InfectionStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- placebo-controlled trial with 1:1:1 enrollment into three arms: inulin 32 g/day, inulin 16 g/day, and placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Freedberg, MD, Columbia University
- Investigators
- Daniel E Freedberg, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865706
- Sponsor's protocol ID
- AAAS2576
- Other IDs
- PR181960
- Status last verified
- Jun 2025
- First submitted
- 4 Mar 2019
- Last updated
- 19 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ma D, Uhlemann AC, Abrams JA, Freedberg DE. Clinical and Culture-Based Predictors of Gut Microbiome Alpha Diversity at the Time of ICU Admission. Crit Care Explor. 2026 Jul 24;8(7):e1455. doi: 10.1097/CCE.0000000000001455. eCollection 2026 Jul 1.
PubMed 42497015Seeram D, Park H, Abrams JA, Uhlemann AC, Freedberg DE. Vancomycin-Resistant Enterococcus Often Spreads From Hospitalized Patients Into the Local Environment and Less Often Spreads From the Environment Into Patients. J Infect Dis. 2026 Aug 3;234(1):20-29. doi: 10.1093/infdis/jiag240.
PubMed 42047567Park 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.
PubMed 40237647Park 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.
PubMed 39806400
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prebiotic Inulin to Limit Antimicrobial-Resistant Infections During Critical Illness: A Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT03865706
- Acronym / sponsor ID
- AAAS2576
- Conditions
- Antibiotic Resistant Infection, Nosocomial Infection, Pathogen Transmission, Nutrition Disorders, Critical Illness, Sepsis
- Keywords
- Microbiome, Antibiotic resistance, Intensive care unit, Sepsis, Nutrition, Pathogen colonization
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 21 Nov 2023 (actual)
- Study completion
- 23 Jul 2024 (actual)
- First posted
- 7 Mar 2019 (actual)
- Results
- Posted 17 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- placebo-controlled trial with 1:1:1 enrollment into three arms: inulin 32 g/day, inulin 16 g/day, and placebo
| Arm | Type | Receives |
|---|---|---|
| Inulin 32 g/day | Experimental | Drug: Inulin Oral Suspension, Drug: Broad-spectrum antibioticsCritically 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 | Experimental | Drug: Inulin Oral Suspension, Drug: Broad-spectrum antibioticsCritically 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 comparator | Drug: Placebo Oral Suspension, Drug: Broad-spectrum antibioticsCritically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inulin Oral SuspensionAlso: InulinInulin 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 | Drug | Inulin 16 g/day, Inulin 32 g/day |
| Placebo Oral SuspensionAlso: Placebo250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor | Drug | Placebo |
| Broad-spectrum antibioticsAlso: AntibioticsStandard of care treatment for infections | Drug | Inulin 16 g/day, Inulin 32 g/day, Placebo |
Primary outcome
Within-individual Change in SCFA Producer Level
Time frame: 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.
2 secondary outcomes
Multidrug Resistant Organism (MDRO)-Gram Negative Bacteria (GNB) Colonization Status
Time frame: Day 0 and at last sample collected, up to Day 30
Vancomycin-resistant Enterococcus (VRE) Colonization Status
Time frame: Day 0 and at last sample collected, up to Day 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42497015Ma D, Uhlemann AC, Abrams JA, Freedberg DE. Clinical and Culture-Based Predictors of Gut Microbiome Alpha Diversity at the Time of ICU Admission. Crit Care Explor. 2026 Jul 24;8(7):e1455. doi: 10.1097/CCE.0000000000001455. eCollection 2026 Jul 1.
- Derived from this study: PubMed 42047567Seeram D, Park H, Abrams JA, Uhlemann AC, Freedberg DE. Vancomycin-Resistant Enterococcus Often Spreads From Hospitalized Patients Into the Local Environment and Less Often Spreads From the Environment Into Patients. J Infect Dis. 2026 Aug 3;234(1):20-29. doi: 10.1093/infdis/jiag240.
- Derived from this study: PubMed 40237647Park 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.
- Derived from this study: PubMed 39806400Park 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel E Freedberg, MD, MS principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inulin Oral Suspension and Broad-spectrum antibiotics in people with Antibiotic Resistant Infection and Nosocomial Infection, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Within-individual Change in SCFA Producer Level (time frame: Baseline and Day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03865706, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2025.