Fecal Microbiota Transplantation for the Treatment of ICU Delirium: An Investigator-Initiated, Prospective, Two-Arm, Single-Center, Non-Blinded, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- Delirium-free days (DFDs)
研究概览
简要总结
Delirium in the intensive care unit (ICU) is a prevalent and serious neurological complication among critically ill patients, with large multicenter studies reporting an incidence of 30% to 80%, particularly in those requiring mechanical ventilation. Delirium is not only associated with prolonged ICU and hospital stays but also with increased morbidity and mortality. Notably, up to 40% of survivors suffer from persistent cognitive dysfunction that may last for months or even years. Despite current standard pharmacological interventions-such as haloperidol and second-generation antipsychotics-failing to demonstrate significant clinical benefit in phase III trials, non-pharmacological strategies remain challenging to implement due to environmental and operational constraints within the ICU. This unmet clinical need underscores the imperative to develop novel, effective therapeutic approaches.
Emerging evidence suggests that ICU-acquired gut microbiota dysbiosis plays a pivotal role in the pathogenesis of delirium. Dysbiosis can compromise intestinal barrier integrity, promoting systemic inflammation and increasing susceptibility to various forms of delirium, including acute illness-related and postoperative types. These effects are likely mediated through the "gut-microbiota-brain axis," which may represent a central mechanism underlying neurocognitive dysfunction in critical illness.
Preclinical studies have demonstrated that fecal microbiota transplantation (FMT) can restore microbial balance and exert beneficial effects on neurological function. FMT has shown promise in ameliorating cognitive deficits in models of Alzheimer's disease, chronic cerebral hypoperfusion, traumatic brain injury, and chronic unpredictable mild stress (CUMS). Clinically, FMT has been associated with cognitive improvement in patients with dementia, recurrent Clostridioides difficile infection, and sepsis-associated encephalopathy. With expanding applications in both gastrointestinal and extraintestinal disorders, FMT has emerged as a transformative therapeutic modality, supported by robust short- and long-term safety and efficacy data.
This study aims to evaluate whether FMT can alleviate delirium severity, correct gut microbiota dysbiosis at 0, 72, and 120 hours post-enrollment, attenuate intestinal barrier dysfunction, reduce systemic inflammation and disease severity, shorten ICU length of stay, and lower rates of ICU mortality, in-hospital mortality, and 28-day all-cause mortality-ultimately positioning FMT as a potential breakthrough intervention for ICU delirium.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Age ≥ 18 years old, no ethnic or gender restrictions;
- •2. CAM-ICU-positive delirium;
- •3. Expected ICU stay ≥ 5 days after inclusion in the study;
- •4. Signed written informed consent.
排除标准
- •1. Routine administration of antipsychotic medications: Conventional antipsychotic therapy refers to the daily ingestion or application of any sustained-release formulation (in any dosage form) of antipsychotic drugs with the ATC code N05A (in any form), including the following agents:
- •Typical antipsychotics: Chlorprothixene, Flupentixol, Haloperidol, Levomepromazine, Loxapine, Melperone, Perphenazine, Pericyazine, Pimozide, Prochlorperazine, Zuclopenthixol, Pimavanserin, Sulpiride.
- •Atypical antipsychotics: Amisulpride, Aripiprazole, Asenapine, Clozapine, Lurasidone, Olanzapine, Paliperidone, Quetiapine, Risperidone, Sertindole, Ziprasidone. However, the non-habitual administration of antipsychotic medications in the general ward prior to the patient's ICU admission (e.g., for the management of delirium) is deemed acceptable. Nevertheless, antipsychotic therapy should be discontinued upon the patient's ICU admission.
- •2. Severe systemic infection in the early stage of resuscitation, hemodynamic instability or insufficient tissue perfusion, and severe imbalance of water, electrolyte and acid-base.
- •3. Patients with a high risk of death within 5 days as judged by the clinician, or those whose treatment decisions are restricted.
- •4. Active major gastrointestinal bleeding, perforation, or other severe damage to the intestinal barrier.
- •5. Patients who cannot tolerate 50% of their caloric requirements through enteral nutrition due to severe diarrhea, significant fibrotic intestinal stenosis, severe gastrointestinal bleeding, or high-flow enteric fistula.
- •6. Planned or recent abdominal surgery (within 14 days).
- •7. Currently diagnosed with fulminant colitis or toxic megacolon.
- •8. Recently received high-risk immunosuppressive or cytotoxic drug treatment: such as rituximab, doxorubicin, or medium to high-dose corticosteroids (20 mg/d prednisone or higher) for more than 4 weeks.
- •9. Pregnant or lactating women.
- •10. Participated in other clinical trials as a subject within the past 3 months or at the time of enrollment.
- •11. Delirium assessment non applicable: this includes language barriers (patients with foreign language where delirium assessment cannot be confidently performed by the site staff), patients who are deaf, blind or aphasic. Comatose patients are not applicable for delirium assessment. Coma is defined by the following levels of consciousness: RASS -4 to -
- •Further, RASS -3 may be considered as coma if this is the judgement of the treating physician. If a patient's coma is considered related to administration of sedative agents, an effort should be made to reduce or terminate the sedative treatment, according to the clinician's discretion.
- •12. Doubtful validity of informed consent: subjects with mental illness, intellectual disability, poor motivation, or other factors that limit the validity of informed consent for participation in this study.
研究组 & 干预措施
Control group
The control group received standard ICU care, which includes monitoring vital signs, managing underlying conditions, infection treatment, nutritional support, and sedation or analgesia as per established clinical guidelines. These patients did not receive fecal microbiota transplantation (FMT). Treatment decisions were made by the attending physician according to standard ICU protocols and routine clinical practice.
FMT intervention Group
FMT was administered via nasojejunal tube in addition to standard ICU care. A volume of 50-100 mL of intestinal microbiota suspension was delivered daily through the nasojejunal tube over a three-day period, between 11:00 and 13:00 each day.
干预措施: Intestinal microbiota suspension (Other)
结局指标
主要结局
Delirium-free days (DFDs)
时间窗: During the first 28 days post-enrollment
The CAM-ICU is a standardized tool specifically designed for the rapid screening of delirium in ICU patients. It achieves efficient diagnosis by evaluating indicators including consciousness state, attention, and disordered thinking. and perceptual abnormalities. Delirium can be diagnosed if features 1 and 2 are met, and at least 3 or 4 are present. The assessment process is standardized, and medical staff can operate independently after training. For patients who survived and were discharged from the ICU or hospital during the study observation period, the entire period subsequent to their discharge date shall be counted as delirium-free. For patients who died during the study observation period, the interval from their date of death to the end of the observation period shall be recorded as 0 delirium-free days. DFDs = Total observation days - Days with delirium - Days with coma - Days from death to the end of observation.
次要结局
- CAM-ICU-7 score(From ICU admission to ICU discharge or death during ICU stay.)
- Changes in intestinal microbiota composition(At 0, 72, and 120 hours post-inclusion)
- Alterations in serum metabolites(At 0, 72, and 120 hours post-inclusion)
- Acute Gastrointestinal Injury (AGI) Score(At 0, 24, 48, 72, 96, and 120 hours post-inclusion)
- APACHE ⅡScore(At 0, 24, 48, 72, 96, and 120 hours post-inclusion)
- Length of stay in the ICU(Up to 4 weeks after inclusion)
- ICU mortality rate(Up to 4 weeks after inclusion)
- In-hospital mortality rate(Up to 4 weeks after inclusion)
- Number of days alive and discharged within 28 days(Up to 28 days after inclusion)
- Number of days survived without mechanical ventilation within 28 days(Up to 28 days after inclusion)
- 28-day all-cause mortality rate(Up to 28 days after inclusion)
研究者
Jiancheng Zhang
Prof. Jiancheng Zhang
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology