Inulin for Infections in the Intensive Care Unit
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: 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
Other Names:
Drug: Broad-spectrum antibiotics
Standard of care treatment for infections
Other Names:
|
| Experimental: 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. |
Drug: 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
Other Names:
Drug: Broad-spectrum antibiotics
Standard of care treatment for infections
Other Names:
|
| Placebo Comparator: Placebo 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
250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor
Other Names:
Drug: Broad-spectrum antibiotics
Standard of care treatment for infections
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Within-individual change in SCFA producer level [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]
relative abundance (i.e., proportion) of SCFA producing bacteria within each treatment group, will be assessed via 16S sequencing of rectal swabs
- MDRO colonization status [ICU Day 3, calculated in a similar manner as outcome 1]
proportion of patients who are MDRO colonized within each treatment group, with MDRO colonization status classified categorically based on the presence or absence of MRSA, VRE, or Gram negative bacteria with CFTX non-susceptibility
- MDR infections [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 CDC/NHSN guideline definitions, and (3) receive appropriate antibiotics from the treating team
Secondary Outcome Measures
- Nutritional intake [through Day 3 and through Day 7]
proportion of goal calories consumed within each treatment group, after adjusting for death
- ICU length of stay (LOS) [through ICU Day 30]
compared between groups, after adjusting for death as a competing risk
- Multi-omic approach to changes related to inulin [outcomes focus on Day 3 and re-analyzed based on Day 7]
overall goal is to understand effects of inulin: will compare SCFA level in whole stools, overall taxonomy, functional metagenomics, metabolomics, and sepsis biomarkers between groups
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 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
Exclusion Criteria:
-
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-TNFα agents, calcineurin inhibitors, or mycophenolate
-
Surgery involving the intestinal lumen within 30 days or known intestinal strictures
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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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Columbia University Medical Center | New York | New York | United States | 10023 |
Sponsors and Collaborators
- Columbia University
Investigators
- Principal Investigator: Daniel E Freedberg, MD, MS, Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AAAS2576