FMT for 90-Day Outcome of Clinical Use in ICU Sepsis

N/ANot Yet RecruitingNCT07670299

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology60 enrolled

Overview

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, representing one of the leading causes of death in intensive care units (ICUs) worldwide. Gut microbiota disruption is increasingly recognized as a key driver of persistent inflammation and multiple organ dysfunction in septic patients. Fecal microbiota transplantation (FMT) has emerged as a promising approach to restore gut microbial homeostasis. This study hypothesizes that FMT acts not through long-term engraftment of donor microbes, but via a "functional pulse" - a potent, transient biological intervention that delivers high-dose microbial metabolites (e.g., short-chain fatty acids), competitively inhibits pathogens, and rapidly modulates intestinal immune cell functions. This is a single-center, open-label, randomized controlled trial conducted in the ICU of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. A total of 60 adult patients diagnosed with sepsis according to Sepsis-3 criteria within 24 hours of ICU admission will be randomized in a 1:1 ratio to receive either ICU standard care alone (control group) or ICU standard care plus FMT administered via a nasojejunal tube for three consecutive days (intervention group). The primary endpoint is all-cause mortality at 90 days. Secondary endpoints include ICU mortality, in-hospital mortality, 28-day mortality, changes in gut microbiota composition and metabolites, serum citrulline levels as a marker of intestinal barrier function, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, vasopressor requirements, C-reactive protein and procalcitonin levels, fluid balance, incidence of ICU delirium and feeding intolerance, and 90-day hospital readmission rate. Safety outcomes include gastrointestinal symptoms and transient fever.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years, any ethnicity, any gender. * Diagnosis of sepsis according to the Sepsis-3 criteria (infection with an acute change in SOFA score ≥ 2 points). * Signed written informed consent. Exclusion Criteria: * Patients whom the attending clinician considers to have a high risk of death within 5 days, or patients with treatment limitations in place. * Active major gastrointestinal bleeding, perforation, or other severe impairment of the intestinal barrier. * Patients unable to tolerate enteral nutrition meeting ≥50% of caloric requirements due to severe diarrhea, significant fibrotic intestinal stricture, severe gastrointestinal bleeding, or high-output intestinal fistula. * Planned or recent abdominal surgery (within 14 days). * Current diagnosis of fulminant colitis or toxic megacolon. * Recent receipt of high-risk immunosuppressive or cytotoxic therapy, such as rituximab, doxorubicin, or moderate-to-high-dose corticosteroids (≥20 mg/day of prednisone or equivalent) for more than 4 consecutive weeks. * Pregnant or breastfeeding women. * Participation in another clinical trial as a subject at the time of enrollment or within 3 months prior to enrollment. * Subjects for whom the validity of informed consent is questionable, including those with psychiatric disorders, intellectual disability, poor motivation, or other conditions that may limit their ability to provide informed consent.

Outcomes

Primary Outcomes

All-Cause Mortality at 90 Days

Proportion of participants who die from any cause within 90 days following enrollment.

Time frame: 90 days post-enrollment

Secondary Outcomes

ICU Mortality

Proportion of participants who die from any cause during their stay in the intensive care unit (ICU).

Time frame: ICU stay, assessed up to 90 days

In-Hospital Mortality

Proportion of participants who die from any cause during the index hospitalization.

Time frame: Hospitalization period, assessed up to 90 days

28-Day All-Cause Mortality

Proportion of participants who die from any cause within 28 days after enrollment.

Time frame: 28 days post-enrollment

Change in Gut Microbiota Composition

Changes in gut microbial community structure assessed by 16S rRNA gene sequencing of fecal samples or rectal swabs, including: (1) alpha diversity (within-sample richness and evenness), (2) beta diversity (between-sample dissimilarity), and (3) alterations in relative abundance of key bacterial taxa at phylum and genus levels.

Time frame: Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT.

Change in Fecal Metabolome

Changes in the fecal metabolic profile, including short-chain fatty acids and other microbial-derived metabolites, assessed using untargeted metabolomics.

Time frame: Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT

Change in serum Metabolome

Changes in the serum metabolic profile, including short-chain fatty acids and other microbial-derived metabolites, assessed using untargeted metabolomics.

Time frame: Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT

Serum Citrulline Concentration

Serial measurements of serum citrulline concentration, an indicator of intestinal epithelial cell mass and enterocyte function.