Critical Illness, Dysbiosis, Fecal Microbiota Transplantation, Gastrointestinal Dysfunction, Sepsis
Conditions
Brief summary
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
OTHERGut 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 suspension administered daily between 11:00 AM and 1:00 PM. Patients are fasting for at least 2 hours before FMT and remain fasting for 2 hours after each administration. The intervention is administered in addition to standard ICU care.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality at 90 Days | 90 days post-enrollment | Proportion of participants who die from any cause within 90 days following enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Mortality | ICU stay, assessed up to 90 days | Proportion of participants who die from any cause during their stay in the intensive care unit (ICU). |
| In-Hospital Mortality | Hospitalization period, assessed up to 90 days | Proportion of participants who die from any cause during the index hospitalization. |
| 28-Day All-Cause Mortality | 28 days post-enrollment | Proportion of participants who die from any cause within 28 days after enrollment. |
| Change in Gut Microbiota Composition | Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT. | 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. |
| Change in Fecal Metabolome | Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT | Changes in the fecal metabolic profile, including short-chain fatty acids and other microbial-derived metabolites, assessed using untargeted metabolomics. |
| Change in serum Metabolome | Baseline (0 hours), 72 hours after the last FMT, and 28 days after the last FMT | Changes in the serum metabolic profile, including short-chain fatty acids and other microbial-derived metabolites, assessed using untargeted metabolomics. |
| Serum Citrulline Concentration | Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment | Serial measurements of serum citrulline concentration, an indicator of intestinal epithelial cell mass and enterocyte function. |
| Change in Sequential Organ Failure Assessment (SOFA) Score | Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment | Change in SOFA score, which ranges from 0 to 24 (higher scores indicate more severe organ dysfunction). |
| Change in Acute Physiology and Chronic Health Evaluation II (APACHE II) Score | Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment | Change in APACHE II score, which ranges from 0 to 71 (higher scores indicate more severe illness and higher mortality risk). |
| Cumulative total dose of vasoactive agents | 7 days post-enrollment | Cumulative total dose of vasoactive agents (expressed as norepinephrine equivalents) administered from enrollment through 7 days post-enrollment. |
| Change in serum level of C-reactive protein (CRP) | Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment | Serial measurements of serum CRP levels. |
| Change in serum level of procalcitonin (PCT) | Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment | Serial measurements of serum PCT levels. |
| Cumulative Fluid Balance | 7 days post-enrollment | Total positive fluid balance (in milliliters) accumulated within 7 days after enrollment. |
| Incidence of ICU Delirium | Up to 7 days post-enrollment (during ICU stay) | Incidence of delirium during the ICU stay, assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). |
| Incidence of Feeding Intolerance | Up to 7 days post-enrollment (during ICU stay) | Incidence of feeding intolerance, defined as the inability to achieve an enteral nutrition target of 20 kcal/(kg·d) within 72 hours due to any clinical reason (e.g., vomiting, diarrhea, or enterocutaneous fistula), or cessation of enteral nutrition for any clinical reason, excluding temporary interruptions for clinical procedures or operational reasons. |
| 90-Day Hospital Readmission Rate | 90 days post-discharge | Proportion of participants readmitted to the hospital for any cause within 90 days after discharge from the index hospitalization. |
| Incidence of FMT-Related Adverse Events | During the FMT administration period (up to 7 days) | Incidence of adverse events potentially associated with FMT, including gastrointestinal symptoms (nausea, vomiting, abdominal pain, abdominal distension, and diarrhea) and transient fever. |
Contacts
CONTACTJiancheng Zhang, MD, PhD
Outcome results
None listed