Open-label, Randomized Study to Assess the Efficacy of a Probiotic or Fecal Microbiota Transplantation (FMT) on the Eradication of Rectal Multidrug-resistant Gram-negative Bacilli (MDR-GNB) Carriage (PROFTMDECOL)
试验速览
- 阶段
- 不适用
- 入组人数
- 437
- 试验地点
- 1
- 主要终点
- Proportion of patients with digestive decolonization rate
研究概览
简要总结
The working hypothesis is that in patients who are rectal carriers of MDR-GNB (Multi drug-resistant gram negative bacilli), the rate and speed of eradication of the carrier status obtained with NAA regimens are insufficient and could be improved with additional interventions directed to restore a healthy fecal microbiota or to increase the colonization resistance by the putative beneficial activity of lactate-producing bacteria and bifidobacteria. A healthier colonic microbiota environment is expected not only to promote the eradication of the existing MDR organisms but also to hinder the subsequent recolonization and hopefully the risk of infection with gut dysbiosis -associated pathogens (MDR-GNB, C. difficile and Candida).
The principal objective of the study is To compare the decolonization efficacy at the end of the study (60 ± 7 days after randomization) of the administration of a probiotic ("Vivomixx®" 2 sachets/12h for 2 weeks) versus the administration of two doses (administered a week apart) of a fecal microbiota transplantation preparation (equivalent to 50 g of healthy donor feces) and no treatment (control arm) in patients with rectal colonization with MDRGNB (ESBL-producing Klebsiella pneumoniae, CPE and MDR/XDR (multi drug-resistant/ extensively drug-resistant Pseudomonas aeruginosa).
详细描述
Data Collection and Processing
Recording of data All data required for the study will be recorded in the participating center using a case report form (CRF). Completeness and plausibility checks will ensure the collection of high quality data.
A CRF for each patient will be completed by authorized personnel who must be identified and authorized in writing by the Principal Investigator before they conduct any study related tasks.
A delegation of responsibility log identifying who can enter data and/or sign off a CRF will be maintained by the Principal Investigator.
The subject's number and date of entry into the study, along with a study identifier, should be recorded in the subject's study records. The following should also be recorded in the study records: confirmation of written consent, the subject's clinical status, date of every study visit, copies of all relevant reports, comments on results and reference to serious adverse events and related adverse events.
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
- •Adult patients (≥18 years-old).
- •Admitted to the Hospital Clinic of Barcelona with documented rectal colonization whitin the previous 7 days by rectal swabbing with MDR-GNB (ESBL-producing Klebsiella pneumoniae, carbapenemase-producing Enterobacterial (CPE) and MDR/XDR Pseudomonas aeruginosa).
- •Eligible for routine digestive decolonization (7 days oral administration of nonabsorbable antibiotics (NAA).
- •Capable to provide informed consent (by themselves or through their legal representatives).
排除标准
- •Pregnant women or breastfeeding.
- •Neutropenic patients (total neutrophil count <500 cell/mm3)*.
- •HIV-infected patients with CD4(cluster of differentiation 4) count <200 cell/mm
- •Patients with active C. difficile infection.
- •Patients with ileus or bowel obstruction.
- •Patients with documented or suspected bowel perforation.
- •Patients with a colistin-resistant MDR-GNB.
- •Solid organ or hematopoietic organ transplant recipients without neutropenia will qualify for inclusion in the study. This is based on preliminary data on the safety of probiotics without Saccharomyces boulardii/cerevisae in transplant recipients of several organs (hematopoietic precursors, liver, kidney, small intestine) and on the preliminary safety data of FMT in nonneutropenic patients with hematological disorders including hematopoietic cell transplantation (25,42,43). However, the condition of transplant recipients will be assessed inan individual basis and only those patients that by consensus with their attending physician will be judged to be at a very low risk of complications derived from the use of the probiotic o fecal microbiota will be considered for inclusion in the study.
研究组 & 干预措施
CONTROL
No intervention arm
FMT REGIMEN
干预措施: FMT REGIMEN (Dietary Supplement)
PROBIOTIC
干预措施: PROBIOTIC (Dietary Supplement)
结局指标
主要结局
Proportion of patients with digestive decolonization rate
时间窗: At the end of study (60 ± 7 days after the randomization).
Proportion of patients with digestive decolonization rate defined as negative rectal swab (RS) for the target MDR-GNB (ESBL-producing Klebsiella pneumoniae, CPE and MDR/XDR Pseudomonas aeruginosa) at the end of study (60 ± 7 days after the randomization).
次要结局
- development of resistance to colistin or amikacin(through study completion, an average of 1 year)
- Changes in fecal microbiota composition(At the end of study treatment (3 weeks after randomization).)
- target MDR-GNB or any other MDR-GNB in any control RS or fecal sample(through study completion, an average of 1 year)
- clinical infections(through study completion, an average of 1 year)
- Digestive decolonization rate defined as a negative fecal sample(At the end of study treatment (3 weeks after randomization).)
- Digestive decolonization rate defined as a negative rectal swab((week 1 after randomization).)
研究者
José Antonio Martinez
MD, PhD, Senior Consultor, Assistant Profesor of Medicine (University of Barcelona)
Hospital Clinic of Barcelona