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

Official title

Fecal Microbiota Transplantation for 90-Day Outcome of Clinical Use in ICU Sepsis: a Single-Center, Open-Label, Randomized Controlled Trial

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.

Interventions

• Other Gut microbiota suspension
  FMT is a biologic intervention that involves the transfer of functional microbiota from the feces of healthy screened donors into the recipient's intestinal tract to restore gut microbial diversity and ecological stability. The FMT product is prepared from 100-150 g of adolescent donor feces, processed into 300 mL of fecal microbiota suspension, with each 50-100 mL. Patients in the intervention group receive FMT via nasojejunal tube on 3 consecutive days, with 50 mL of fecal microbiota suspensio

Primary outcome measures

• All-Cause Mortality at 90 Days [Time frame: 90 days post-enrollment]

Secondary outcome measures (12)

• ICU Mortality [Time frame: ICU stay, assessed up to 90 days]
• In-Hospital Mortality [Time frame: Hospitalization period, assessed up to 90 days]
• 28-Day All-Cause Mortality [Time frame: 28 days post-enrollment]
• Change in Gut Microbiota Composition [Time frame: Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT.]
• Change in Fecal Metabolome [Time frame: Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT]
• Change in serum Metabolome [Time frame: Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT]
• Serum Citrulline Concentration [Time frame: Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment]
• Change in Sequential Organ Failure Assessment (SOFA) Score [Time frame: Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment]
• Change in Acute Physiology and Chronic Health Evaluation II (APACHE II) Score [Time frame: Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment]
• Cumulative total dose of vasoactive agents [Time frame: 7 days post-enrollment]
• Change in serum level of C-reactive protein (CRP) [Time frame: Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment]
• Change in serum level of procalcitonin (PCT) [Time frame: Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07670299 · zjc202601

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗