Inulin for Infections in the Intensive Care Unit

Sepsis Clinical Trial

Official title:

Prebiotic Inulin to Limit Antimicrobial-Resistant Infections During Critical Illness: A Phase II Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03865706
• Other study ID #: AAAS2576
• Secondary ID: PR181960
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 14, 2019
• Est. completion date: September 30, 2024

Study information

• Verified date: May 2024
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: September 30, 2024
• Est. primary completion date: November 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Hospitalized in an eligible medical ICU

2. Age = 18 years old at the time of hospitalization

3. 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

4. Received broad-spectrum antibiotics within the last 24 hours or ordered and pending administration

5. Able to complete enrollment within 4 hours of ICU admission for administration of the intervention within 6 hours of ICU admission

Exclusion Criteria:

1. Inability to receive oral or enteric fluids

2. Inulin allergy

3. Hyponatremia (serum sodium =128 mEq/L)

4. 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-TNFa agents, calcineurin inhibitors, or mycophenolate

5. Surgery involving the intestinal lumen within 30 days or known intestinal strictures

6. Do Not Resuscitate (DNR) or Do Not Intubate (DNI) status, or "no escalation of care" orders

7. Lack capacity for consent and no appropriate Legally Authorized Representative (LAR)

Related Conditions & MeSH terms

• Antibiotic Resistant Infection
• Communicable Diseases
• Critical Illness
• Cross Infection
• Infections
• Nosocomial Infection
• Nutrition Disorders
• Pathogen Transmission
• Sepsis

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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
Primary	MDRO colonization status	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	ICU Day 3, calculated in a similar manner as outcome 1
Primary	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 CDC/NHSN guideline definitions, and (3) receive appropriate antibiotics from the treating team	through 30 days
Secondary	Nutritional intake	proportion of goal calories consumed within each treatment group, after adjusting for death	through Day 3 and through Day 7
Secondary	ICU length of stay (LOS)	compared between groups, after adjusting for death as a competing risk	through ICU Day 30
Secondary	Multi-omic approach to changes related to inulin	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	outcomes focus on Day 3 and re-analyzed based on Day 7