A Randomised, Controlled, Open-label Phase III Clinical Trial in Patients With Primary or Recurrent Clostridioides Difficile (CD) Infection, to Evaluate the Efficacy and Safety of Capsules of Lyophilised Faecal Microbiota vs Fidaxomicin.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 21
- 主要终点
- Global Absence of Diarrhea Due to Clostridiodes Difficile 8 Weeks After the Start of the Treatment
研究概览
简要总结
Patients with microbiota alterations developed after being exposed to antibiotics are especially susceptible to Clostridioides difficile infections (CDI). The incidence and severity of CDI has increased in recent years and CDI recurrences (r-CDI) due to the appearance of new episodes in patients with a previous cured CDI, represent a serious and complex clinical issue. Although antibiotics are the recommended therapy for the first episode of CDI, treatment with oral vancomycin and/or metronidazole often results in significant treatment failure. In addition, the treatment of r-CDI is not adequately standardized, and although the most widely used treatment is the administration of fidaxomicin and bezlotoxumab, its efficacy in patients who already have r-CDI is not proven. In the late years, Fecal Microbiota Transfer (FMT) has emerged as the preferred non-pharmacological treatment to manage CDI with multiple recurrences and recent clinical trials have evaluated its potential efficacy and safety in the treatment of patients with primary CD infection.
The objective of this study is to assess the efficacy and safety of the MBK-01 medication, consisting of heterologous lyophilized fecal microbiota capsules coming from healthy donors in comparison to the treatment with fidaxomicin, in 92 patients with primary or r-CDI.
详细描述
This is a Phase III, multicenter, controlled and open label clinical trial in which patients who suffered an episode of Clostridioides difficile infection (either the first episode or subsequent recurrences) will be randomly assigned (1:1) to one of the following arms:
- Fidaxomicin
- MBK-01 (heterologous lyophilized fecal microbiota)
Objective: To assess the efficacy of FMT with capsules of lyophilized fecal microbiota (MBK-01), compared to the control (fidaxomicin) at 8 weeks after the start of the treatment. Also, assess the safety of MBK-01 and the quality of life of patients participating in the study.
Follow up: participants will return for clinic visits at 72 hours, week 3 and week 8 after the start of the treatment, and will receive follow-up phone calls at month 3 and month 6 after the start of the treatment. Stool samples will be collected from participants for further studies at time 0 and week 8 after the start of the treatment. Study Outcomes are detailed in the specific section of this website.
Rationale: The transferred microbiota restores the recipient's intestinal microbiota by reintroducing bacterial taxa that were absent or in low proportion in the recipient before the FMT. This supports the expansion of the recipient's own commensal microbiota and re-establishing a microbiota community with a high biodiversity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of both genders, over 18 years.
- •Patients that undergo an episode of CD infection (either the first episode or subsequent recurrences).
- •Presence of an episode of diarrhea defined as ≥3 stools/24 hours, at the beginning of the episode.
- •Confirmation of the presence of CD toxin A and/or B in faeces, by a direct toxin detection test or by the PCR technique for the detection of toxin/s producing genes, at the start of the episode that is going to be treated in the clinical trial (the toxin test must be positive within 7 days prior to the enrolment of the patient in the trial).
排除标准
- •Previous faecal microbiota transfer.
- •Transplanted patients, except those with a solid organ transplant of more than 2 years, with good organ function.
- •Absolute neutrophil count <500 cells /μL at the time of the enrollment in the study.
- •Pregnancy, breastfeeding, or pregnancy intentions over the course of the study.
- •Active treatment with bile acid sequestrants (for instance: cholestyramine).
- •Positive patients for the human immunodeficiency virus (HIV) except those with lymphocytes T CD4 count > 200 cells/μL and viral load less than 20 copies.
- •Swallowing dysfunction or no oral motor coordination.
- •Patient admitted in an intensive care unit or expected to be admitted in an intensive care unit due to serious illness.
- •History of significant medical conditions that, in the opinion of the investigator, would not allow an adequate evaluation or follow-up of the patient.
研究组 & 干预措施
MBK-01
Participants will receive MBK-01 capsules of fecal microbiota coming from healthy donors (45 patients).
干预措施: MBK-01 (Biological)
Fidaxomicin
Participants will receive Fidaxomicin (47 patients).
干预措施: Fidaxomicin (Drug)
结局指标
主要结局
Global Absence of Diarrhea Due to Clostridiodes Difficile 8 Weeks After the Start of the Treatment
时间窗: 8 weeks after the start of the treatment
Number of patients who showed recurrence of at least one Episode of Diarrhea (3 or More Stools/24 Hours) 8 Weeks After the Start of the Treatment. Recurrence is understood as the reappearance of clinical manifestations of a new episode of CDI that re-occurs within 8 weeks after the onset of symptoms of a previous episode that was resolved.
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 72 Hours After the Start of the Treatment
时间窗: 72 hours after the start of the treatment
Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 3 Weeks After the Start of the Treatment
时间窗: 3 weeks after the start of the treatment
Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 3 Months After the Start of the Treatment
时间窗: 3 months after the start of the treatment
Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 6 Months After the Start of the Treatment
时间窗: 6 months after the start of the treatment
Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.
次要结局
- Duration of Hospitalisation(Up to 8 weeks after the start of the treatment)
- Good/Bad Progress of the Patient(Up to 72 hours after the start of the treatment)
- Time to Recurrence Depending on Randomisation Groups(Up to 6 months after the start of the treatment)
- Duration of Treatment(Up to 10 days)
- Overall Survival(Up to 6 months after the start of the treatment)
- Number of Adverse Events Per Randomisation Group(Up to 6 months after the start of the treatment)
- Type of Adverse Events Per Ramdomisation Group(Up to 6 months after the start of the treatment)
- Number of Serious Adverse Events Per Ramdomisation Group(Up to 6 months after the start of the treatment)
- Type of Serious Adverse Events Per Ramdomisation Group(Up to 6 months after the start of the treatment)
- Adverse Events Related to the Treatment(Up to 6 months after the start of the treatment)
- Adverse Event Seriousness(Up to 6 months after the start of the treatment)
- Adverse Events Related to the CDI(Up to 6 months after the start of the treatment)
- Mortality Associated With CDI(Up to 6 months after the start of the treatment)
- Intensive Care Unit Admissions (ICU)(Up to 6 months after the start of the treatment)
- Adverse Events of Special Interest(Up to 6 months after the start of the treatment)
- SF36 Questionnaire (The Short Form-36 Health Survey) to Evaluate the Quality of Life(Day 0, 8 weeks and 6 months after the start of the treatment)