Clinical trial NCT06970262: The Effects of FMT on Intestinal Microbiota and Pulmonary Microecology
Official title: The Effects of Fecal Microbiota Transplantation on Intestinal Microbiota and Pulmonary Microecology in Critically Ill Patients With Multidrug-Resistant Organisms (MDROs) Infections: A Single-Center, Open-Label, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Infection
Microbial Colonization
Food Intolerance Syndromes
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2025-05-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: At present, carbapenem-resistant Enterobacteriaceae (CROs) infections are a global challenge. The use of antibiotics, proton pump inhibitors, and vasoconstrictors in the intensive care unit (ICU), as well as the disease state, have a significant impact on the intestinal flora and may also have a significant impact on the pulmonary microecology, which is unfavorable for the long-term prognosis of patients. The study of pulmonary microecology is currently a hot topic, but it is not clear whether intestinal flora disorders promote pulmonary microecological disorders. Therefore, it is also unclear whether intestinal flora disorders in patients with severe CRO infections have an impact on pulmonary microecological disorders. This project aims to first study the differences in intestinal flora and pulmonary microecology between patients with pulmonary CRO infections and those without CRO infections, as well as the correlation between intestinal flora disorders and pulmonary microecology.

Fecal microbiota transplantation (FMT) is a therapeutic approach that involves transplanting the functional intestinal microbiota from healthy individuals into patients to restore an imbalanced intestinal microbiota and treat intestinal and extra-intestinal diseases. Studies have shown that FMT has a positive effect on the clearance of CROs colonization and the prevention of infection in non-ICU patients. Over the past decade, FMT has made breakthrough progress in the treatment of intestinal and extra-intestinal diseases, bringing disruptive new strategies for the treatment of difficult intestinal and extra-intestinal diseases. These results suggest that FMT not only helps to restore a healthy intestinal microbiota but may also reduce the occurrence of recurrent infections by inhibiting the competition of drug-resistant bacteria. Given that CROs in the intestinal microbiota are an important source of enterogenic infections and hospital-acquired bloodstream infections and pneumonia, this project aims to further conduct a randomized controlled clinical study, including critically ill patients with MDROs infections admitted to the ICU, who can be evaluated to discontinue antibiotics and have food intolerance syndrome. FMT will be administered through a nasojejunal tube to improve the imbalance of the intestinal microbiota caused by broad-spectrum antibiotics and other disturbances, and to study the promoting effect and safety of FMT on the recovery of pulmonary microecological imbalance in critically ill patients, as well as to evaluate its impact on ICU stay, ICU mortality, in-hospital mortality, and 28-day mortality.


Eligibility criteria: The initial step involves investigating the alterations in pulmonary and intestinal microbiota among ICU patients infected with CROs, as well as the correlation between these changes.

Inclusion Criteria:

1. Age ranging from 18 to 70 years old;
2. ICU patients. Gender and ethnicity are not restricted;
3. Informed consent obtained.

Exclusion Criteria:

1. Airway antibiotics (administered via nebulization or intravenous infusion) have been utilized since the current hospitalization;
2. Pulmonary infection caused by non-bacterial pathogens, such as viruses, fungi, or atypical organisms;
3. Infections located outside the pulmonary system, including those in the bloodstream, abdominal cavity, or urinary tract;
4. Respiratory failure secondary to non-pulmonary infections, such as cardiogenic factors or sepsis-like syndromes;
5. Chronic pulmonary conditions, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, and pulmonary interstitial fibrosis;
6. Chronic gastrointestinal disorders, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and non-alcoholic fatty liver disease (NAFLD);
7. Recent surgical procedures involving the abdomen or lungs (within 14 days prior to admission);
8. Pregnant or breastfeeding individuals;
9. Participation in other clinical trials within three months prior to enrollment;
10. Lack of a signed written informed consent form.

Based on the inclusion and exclusion criteria of the first step of the study, further screening was conducted to investigate the promoting effect and safety of fecal microbiota transplantation (FMT) on the recovery of pulmonary microecological imbalance in critically ill patients, and to evaluate its impact on the length of stay in the intensive care unit (ICU), ICU mortality, in-hospital mortality, and 28-day mortality, etc.

Inclusion Criteria:

1. Patients who have been admitted to the ICU for at least 24 hours;
2. An anticipated ICU stay of at least 7 days following enrollment in the study;
3. Diagnosed with food intolerance syndrome.

Exclusion Criteria:

1. Severe systemic infection during the early resuscitation phase, characterized by hemodynamic instability, inadequate tissue perfusion, or severe water, electrolyte, and acid-base imbalance;
2. Patients identified by clinicians as having a high risk of death within 5 days or those subject to restricted treatment decisions;
3. Significant intestinal barrier compromise due to conditions such as active gastrointestinal hemorrhage or perforation;
4. Patients receiving enteral nutrition who are unable to tolerate 50% of their caloric requirements due to significant fibrotic intestinal stenosis, high-output enteric fistulae, or other reasons;
5. Planned abdominal surgery within 14 days;
6. Individuals currently diagnosed with fulminant colitis or toxic megacolon;
7. Neutropenia (neutrophil count \< 1500 cells/µL);
8. Patients with congenital or acquired immunodeficiency disorders;
9. Autoimmune diseases;
10. Hematological malignancies;
11. Individuals who have recently undergone treatment with high-risk immunosuppressive or cytotoxic agents, including rituximab, doxorubicin, or medium-to-high dose steroid hormones (e.g., prednisone ≥ 20 mg/day for more than 4 weeks).

Primary outcomes:
measure: Changes in gut microbiota diversity and metabolic biomarkers
timeFrame: Within 24 hours before FMT intervention, and on days 3, 5, and 7 after inclusion
measure: Changes in pulmonary microecology diversity and metabolic biomarkers
timeFrame: Within 24 hours before FMT intervention, and on days 3, 5, and 7 after inclusion
Secondary outcomes:
measure: Correlation between gut microbiota and pulmonary microecology
timeFrame: Within 24 hours before FMT intervention, and on days 3, 5, and 7 after inclusion
measure: Serum lipopolysaccharide (LPS)
timeFrame: Within 24 hours before FMT intervention, and on days 1-3, 5, and 7 after inclusion
measure: Serum diamine oxidase (DAO)
timeFrame: Within 24 hours before FMT intervention, and on days 1-3, 5, and 7 after inclusion
measure: Serum D-lactic acid
timeFrame: Within 24 hours before FMT intervention, and on days 1-3, 5, and 7 after inclusion
measure: APACHE Ⅱ score
timeFrame: Within 24 hours before FMT intervention, and on days 1-7 after inclusion
measure: The use of vasoactive drugs
timeFrame: Within 24 hours before FMT intervention, and on days 1-7 after inclusion
measure: Serum C-reactive protein
timeFrame: Within 24 hours before FMT intervention, and on days 1-7 after inclusion
measure: Serum procalcitonin
timeFrame: Within 24 hours before FMT intervention, and on days 1-7 after inclusion
measure: Peripheral blood cytokines
timeFrame: Within 24 hours before FMT intervention, and on days 5, and 7 after inclusion
measure: Peripheral blood lymphocyte subsets
timeFrame: Within 24 hours before FMT intervention, and on days 5, and 7 after inclusion
measure: Length of stay in the ICU
timeFrame: From date of randomization until the date of discharge from the ICU or date of death from any cause during ICU stay, whichever came first, assessed up to 6 weeks
measure: ICU mortality rate
timeFrame: From date of randomization until the date of discharge from the ICU or date of death from any cause during ICU stay, whichever came first, assessed up to 6 weeks
measure: In-hospital mortality rate
timeFrame: From date of randomization until the date of discharge from the hospital or date of death from any cause during hospitalization, whichever came first, assessed up to 6 weeks
measure: 28-day mortality rate
timeFrame: Time interval from hospital admission to mortality within 28 days post-hospitalization
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study officials:
References: