New Treatment Strategy for Patients With Multiple Recurrent Clostridioides Difficile Infection With Bezlotoxumab as First Option
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 试验地点
- 4
- 主要终点
- Global cure of the treatment strategy
研究概览
简要总结
The objective of this trial is to investigate whether a treatment strategy offering bezlotoxumab before FMT in patients suffering from multiple recurrent CDI results in equal efficacy compared with a treatment strategy with initial FMT. Strategy A includes bezlotoxumab as ancillary treatment as first option, and FMT in case of failure. Option B includes FMT as ancillary treatment as first option, and antibiotic treatment with fidaxomicin in case of failure. A secondary objective is to provide a point estimate of recurrence after bezlotoxumab for the treatment of multiple recurrent CDI.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-90 years old
- •diarrhea (3 or more unformed stools per 24h for two consecutive days; or >= 8 unformed stools per 48h) XML File Identifier: KqQEbBLRYEZjGgsIl5GcI+NXCyM= Page 10/22
- •positive PCR test for toxin A/B genes and/or positive toxin EIA for current and previous episodes (low PCR cycle threshold value when only PCR performed)
- •a minimum of two prior CDI episodes
- •previous episode is maximum of 3 months prior to the current episode
- •the current episode responds well to Standard of Care treatment (vancomycin or fidaxomicin orally).
- •Assessment of the severity of the disease will be performed according to the ESCMID recommendations.
- •Both mild and severe CDI will be included
排除标准
- •Severe complicated CDI, i.e presence of: hypotension, septic shock, elevated serum lactate, ileus, toxic megacolon, bowel perforation, or any fulminant course of disease.
- •ICU admission for underlying disease
- •pregnancy or current desire for pregnancy
- •breastfeeding
- •(prolonged) use of antibiotics (other than for treatment of CDI) during the study period or directly after the intervention
- •previous use of bezlotoxumab or fecal microbiota transplantation
- •a history of underlying congestive heart failure (potential safety signal phase-III trail bezlotoxumab).
- •Diagnosis of inflammatory bowel disease in medical history.
研究组 & 干预措施
Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy.
initial bezlotoxumab in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 14 days of vancomycin 125mg QID plus fecal microbiota in case of treatment failure.
干预措施: Bezlotoxumab (Drug)
Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy.
initial bezlotoxumab in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 14 days of vancomycin 125mg QID plus fecal microbiota in case of treatment failure.
干预措施: Vancomycin oral (Drug)
Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy.
fecal microbiota transplantation in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 10 days of fidaxomicin 200 mg BID in case of treatment failure.
干预措施: Fecal Microbiota Transplantation (FMT) (Procedure)
Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy.
fecal microbiota transplantation in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 10 days of fidaxomicin 200 mg BID in case of treatment failure.
干预措施: Vancomycin oral (Drug)
结局指标
主要结局
Global cure of the treatment strategy
时间窗: 12 weeks (after rescue therapy if applicable)
Defined as cure without relapse of CDI within 12 weeks after completion of the treatment strategy in the study arm, i.e. after completion of secondary treatment in case of failure on initial treatment.
次要结局
- Post-treatment IBS-like symptoms(12 weeks)
- Fecal microbiota (16S) alfa- and beta-diversity(Pre-treatment and 3 and 12 weeks)
- Cost-effectiveness(12 weeks)
- Initial cure after treatment with bezlotoxumab or FMT(2 days after end of treatment)
- Rate of antibiotic use(12 weeks)
- Recurrence after initial treatment with bezlotoxumab or FMT(12 weeks)
- Sustained cure after initial treatment with bezlotoxumab or FMT(12 weeks)
- Adverse events(12 weeks)
- Duration of hospitalization(12 weeks)
- Eradication of toxigenic C. difficile(3 and 12 weeks)
研究者
Joffrey van Prehn, MD, PhD
Clinical Microbiologist
Leiden University Medical Center