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Inulin for Infections in the Intensive Care Unit

Primary Purpose

Antibiotic Resistant Infection, Nosocomial Infection, Pathogen Transmission

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Inulin Oral Suspension

Placebo Oral Suspension

Broad-spectrum antibiotics

About this trial

This is an interventional prevention trial for Antibiotic Resistant Infection focused on measuring Microbiome, Antibiotic resistance, Intensive care unit, Sepsis, Nutrition, Pathogen colonization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
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)

Sites / Locations

Columbia University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Inulin 32 g/day

Inulin 16 g/day

Placebo

Arm Description

Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.

Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.

Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.

Outcomes

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

Nutritional intake

proportion of goal calories consumed within each treatment group, after adjusting for death

ICU length of stay (LOS)

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

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

Full Information

NCT ID

NCT03865706

First Posted

March 4, 2019

Last Updated

October 11, 2022

Sponsor

Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT03865706

Brief Title

Inulin for Infections in the Intensive Care Unit

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 14, 2019 (Actual)

Primary Completion Date

April 1, 2024 (Anticipated)

Study Completion Date

October 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Antibiotic Resistant Infection, Nosocomial Infection, Pathogen Transmission, Nutrition Disorders, Critical Illness, Sepsis

Keywords

Microbiome, Antibiotic resistance, Intensive care unit, Sepsis, Nutrition, Pathogen colonization

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

placebo-controlled trial with 1:1:1 enrollment into three arms: inulin 32 g/day, inulin 16 g/day, and placebo

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

double-blind, randomized

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Inulin 32 g/day

Arm Type

Experimental

Arm Description

Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (16g twice daily) for a minimum of 7 days.

Arm Title

Inulin 16 g/day

Arm Type

Experimental

Arm Description

Critically ill adults who are receiving broad-spectrum antibiotics will also receive inulin oral suspension (8g twice daily) for a minimum of 7 days.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Critically ill adults who are receiving broad-spectrum antibiotics will also receive placebo oral suspension for a minimum of 7 days.

Intervention Type

Drug

Intervention Name(s)

Inulin Oral Suspension

Other Intervention Name(s)

Inulin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Suspension

Other Intervention Name(s)

Placebo

Intervention Description

250cc sterile water alone, given twice daily a sweetener is added to the water to create identical flavor

Intervention Type

Drug

Intervention Name(s)

Broad-spectrum antibiotics

Other Intervention Name(s)

Antibiotics

Intervention Description

Standard of care treatment for infections

Primary Outcome Measure Information:

Title

Within-individual change in SCFA producer level

Description

relative abundance (i.e., proportion) of SCFA producing bacteria within each treatment group, will be assessed via 16S sequencing of rectal swabs

Time Frame

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

Title

MDRO colonization status

Description

Time Frame

ICU Day 3, calculated in a similar manner as outcome 1

Title

MDR infections

Description

Time Frame

through 30 days

Secondary Outcome Measure Information:

Title

Nutritional intake

Description

proportion of goal calories consumed within each treatment group, after adjusting for death

Time Frame

through Day 3 and through Day 7

Title

ICU length of stay (LOS)

Description

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

Time Frame

through ICU Day 30

Title

Multi-omic approach to changes related to inulin

Description

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

Time Frame

outcomes focus on Day 3 and re-analyzed based on Day 7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Daniel E Freedberg, MD, MS

Phone

8579989370

def2004@cumc.columbia.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Elissa Lynch

el2888@cumc.columbia.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel E Freedberg, MD, MS

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10023

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel E Freedberg, MD, MS

def2004@cumc.columbia.edu

First Name & Middle Initial & Last Name & Degree

Daniel E Freedberg, MD, MS

12. IPD Sharing Statement

Plan to Share IPD

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