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Trial record 17 of 259 for:    Anti-Infective Agents AND Antibiotics, Antitubercular AND broad

Inulin for Infections in the Intensive Care Unit

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ClinicalTrials.gov Identifier: NCT03865706
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Daniel Freedberg, Columbia University

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
Antibiotic Resistant Infection Nosocomial Infection Pathogen Transmission Nutrition Disorders Critical Illness Sepsis Drug: Inulin Oral Suspension Drug: Placebo Oral Suspension Drug: Broad-spectrum antibiotics 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double-blind, randomized
Primary Purpose: Prevention
Official Title: Prebiotic Inulin to Limit Antimicrobial-Resistant Infections During Critical Illness: A Phase II Clinical Trial
Actual Study Start Date : October 14, 2019
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : October 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics
Drug Information available for: Inulin

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 Name: Inulin

Drug: Broad-spectrum antibiotics
Standard of care treatment for infections
Other Name: Antibiotics

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 Name: Inulin

Drug: Broad-spectrum antibiotics
Standard of care treatment for infections
Other Name: Antibiotics

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 Name: Placebo

Drug: Broad-spectrum antibiotics
Standard of care treatment for infections
Other Name: Antibiotics




Primary Outcome Measures :
  1. Within-individual change in SCFA producer level [ 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 ]
    relative abundance (i.e., proportion) of SCFA producing bacteria within each treatment group, will be assessed via 16S sequencing of rectal swabs

  2. MDRO colonization status [ Time Frame: 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

  3. MDR infections [ Time Frame: 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 :
  1. Nutritional intake [ Time Frame: through Day 3 and through Day 7 ]
    proportion of goal calories consumed within each treatment group, after adjusting for death

  2. ICU length of stay (LOS) [ Time Frame: through ICU Day 30 ]
    compared between groups, after adjusting for death as a competing risk

  3. Multi-omic approach to changes related to inulin [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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-TNFα 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03865706


Contacts
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Contact: Daniel E Freedberg, MD, MS 8579989370 def2004@cumc.columbia.edu
Contact: Dagmara Moscoso 9145104792 dim2115@cumc.columbia.edu

Locations
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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10023
Contact: Daniel E Freedberg, MD, MS       def2004@cumc.columbia.edu   
Principal Investigator: Daniel E Freedberg, MD, MS         
Sponsors and Collaborators
Columbia University
Investigators
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Principal Investigator: Daniel E Freedberg, MD, MS Columbia University

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Responsible Party: Daniel Freedberg, Assistant Professor of Medicine and Epidemiology, Columbia University
ClinicalTrials.gov Identifier: NCT03865706     History of Changes
Other Study ID Numbers: AAAS2576
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniel Freedberg, Columbia University:
Microbiome
Antibiotic resistance
Intensive care unit
Sepsis
Nutrition
Pathogen colonization
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Infection
Communicable Diseases
Cross Infection
Nutrition Disorders
Critical Illness
Pathologic Processes
Disease Attributes
Iatrogenic Disease