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| ID | Type | Description | Link |
|---|---|---|---|
| PR181960 | Other Grant/Funding Number | Department of Defense |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Placebo | Placebo Comparator | Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Day 0 and at last sample collected, up to Day 30 |
| Measure | Description | Time Frame |
|---|---|---|
| Fecal Short Chain Fatty Acid (SCFA) Levels | 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. | Days 3 and 7 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel E Freedberg, MD, MS | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Medical Center | New York | New York | 10023 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40237647 | Derived | 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. | |
| 39806400 | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days. Placebo Oral Suspension: 250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor Broad-spectrum antibiotics: Standard of care treatment for infections |
| FG001 | Inulin 16 g/Day | 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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections |
| FG002 | Inulin 32 g/Day | 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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days. Placebo Oral Suspension: 250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor Broad-spectrum antibiotics: Standard of care treatment for infections |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Median | Inter-Quartile Range | percentage of SCFA producers | Baseline and Day 3 |
|
Up to Day 90
Due to the severity of illness in this population (ICU patients with sepsis), only pre-specified adverse events of interest and unanticipated problems that meet the definition of a serious adverse event were collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days. Placebo Oral Suspension: 250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor Broad-spectrum antibiotics: Standard of care treatment for infections |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bloating | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniel E. Freedberg, MD, MS | Columbia University | 857-998-9370 | def2004@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 24, 2020 | Nov 21, 2024 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D003428 | Cross Infection |
| D009748 | Nutrition Disorders |
| D016638 | Critical Illness |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D007444 | Inulin |
| D000900 | Anti-Bacterial Agents |
| ID | Term |
|---|---|
| D013213 | Starch |
| D005936 | Glucans |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 |
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placebo-controlled trial with 1:1:1 enrollment into three arms: inulin 32 g/day, inulin 16 g/day, and placebo
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double-blind, randomized
|
| Placebo Oral Suspension | Drug | 250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor |
|
|
| Broad-spectrum antibiotics | Drug | Standard of care treatment for infections |
|
|
| 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) | Day 0 and at last sample collected, up to Day 30 |
| ICU Length of Stay (LOS) | compared between groups, after adjusting for death as a competing risk | through ICU Day 30 |
| Multidrug Resistant (MDR) Infections | 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 | through 30 days |
| Mortality | 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. | Day 90 |
| BG001 |
| Inulin 16 g/Day |
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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections |
| BG002 | Inulin 32 g/Day | 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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Inulin 16 g/Day |
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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections |
| OG002 | Inulin 32 g/Day | 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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections |
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | Day 0 and at last sample collected, up to Day 30 |
|
|
|
| Other Pre-specified | Fecal Short Chain Fatty Acid (SCFA) Levels | 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. | Posted | Median | Inter-Quartile Range | mMol | Days 3 and 7 |
|
|
|
| Other Pre-specified | ICU Length of Stay (LOS) | compared between groups, after adjusting for death as a competing risk | Posted | Median | Inter-Quartile Range | days | through ICU Day 30 |
|
|
|
| Other Pre-specified | Multidrug Resistant (MDR) Infections | 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 | Posted | Count of Participants | Participants | through 30 days |
|
|
|
| Other Pre-specified | Mortality | 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. | Posted | Count of Participants | Participants | Day 90 |
|
|
|
| Secondary | 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) | Posted | Count of Participants | Participants | Day 0 and at last sample collected, up to Day 30 |
|
|
|
| 7 |
| 30 |
| 0 |
| 30 |
| 15 |
| 30 |
| EG001 | Inulin 16 g/Day | 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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections | 7 | 30 | 0 | 30 | 11 | 30 |
| EG002 | Inulin 32 g/Day | 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 Oral Suspension: 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 Broad-spectrum antibiotics: Standard of care treatment for infections | 9 | 30 | 0 | 30 | 15 | 30 |
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Culture Proven Infection | Infections and infestations | Non-systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D009750 | Nutritional and Metabolic Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| Macromolecular Substances |
| D004040 | Dietary Carbohydrates |
| D002241 | Carbohydrates |
| D005630 | Fructans |
| D011134 | Polysaccharides |
| D000890 | Anti-Infective Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
|
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