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

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

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 Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Critical Illness; Dysbiosis; Gastrointestinal Dysfunction; Fecal Microbiota Transplantation
• Intervention / Treatment: Other: Gut microbiota suspension

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiancheng Zhang, MD, PhD; Phone Number: 13554105815; Email: zhjcheng1@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Participants in this arm will receive standard ICU care according to current clinical guidelines and standard practice, including vital sign monitoring, treatment of underlying diseases, nutritional support, and sedation/analgesia management. Participants will not receive fecal microbiota transplantation (FMT).
Experimental: FMT Intervention Group; Participants in this arm will receive standard ICU care plus FMT administered via a nasojejunal tube. FMT will be given once daily for 3 consecutive days, with 50-100 mL of fecal microbiota suspension administered between 11:00 and 13:00 each day. No oral antibiotics are allowed during the FMT period.	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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Mortality at 90 Days	Proportion of participants who die from any cause within 90 days following enrollment.	90 days post-enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Mortality	Proportion of participants who die from any cause during their stay in the intensive care unit (ICU).	ICU stay, assessed up to 90 days
In-Hospital Mortality	Proportion of participants who die from any cause during the index hospitalization.	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.	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.	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.	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.	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.	Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment
Change in Sequential Organ Failure Assessment (SOFA) Score	Change in SOFA score, which ranges from 0 to 24 (higher scores indicate more severe organ dysfunction).	Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment
Change in Acute Physiology and Chronic Health Evaluation II (APACHE II) Score	Change in APACHE II score, which ranges from 0 to 71 (higher scores indicate more severe illness and higher mortality risk).	Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment
Cumulative total dose of vasoactive agents	Cumulative total dose of vasoactive agents (expressed as norepinephrine equivalents) administered from enrollment through 7 days post-enrollment.	7 days post-enrollment
Change in serum level of C-reactive protein (CRP)	Serial measurements of serum CRP levels.	Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment
Change in serum level of procalcitonin (PCT)	Serial measurements of serum PCT levels.	Baseline, 24, 48, 72, 96, 120, 144, and 168 hours post-enrollment
Cumulative Fluid Balance	Total positive fluid balance (in milliliters) accumulated within 7 days after enrollment.	7 days post-enrollment
Incidence of ICU Delirium	Incidence of delirium during the ICU stay, assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).	Up to 7 days post-enrollment (during ICU stay)
Incidence of Feeding Intolerance	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.	Up to 7 days post-enrollment (during ICU stay)
90-Day Hospital Readmission Rate	Proportion of participants readmitted to the hospital for any cause within 90 days after discharge from the index hospitalization.	90 days post-discharge
Incidence of FMT-Related Adverse Events	Incidence of adverse events potentially associated with FMT, including gastrointestinal symptoms (nausea, vomiting, abdominal pain, abdominal distension, and diarrhea) and transient fever.	During the FMT administration period (up to 7 days)

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): October 15, 2028

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Critical Illness; Sepsis; Dysbiosis
• Other Study ID Numbers: zjc202601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No