Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP): a Multi-centre, Randomized, Placebo-controlled Feasibility Pilot Trial
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 100
- 试验地点
- 4
- 主要终点
- Adherence to MET-2/placebo for the treatment duration
研究概览
简要总结
ARO-DECAMP is a multi-centre, placebo-controlled, pilot and feasibility randomized controlled trial for the microbial consortium Microbial Ecosystem Therapeutic-2. Non-intensive care unit patients ≥ 18 years old diagnosed with a bloodstream infection and receiving treatment for an antibiotic resistant organism will be included. Participants will be randomized to receive either MET-2 or placebo for 10 days. Recruitment rate and study intervention adherence will be evaluated for feasibility. Participants will be followed for 180 days, and biological samples will be collected periodically for clinical, ecological, and biomarker outcomes.
详细描述
Reconstituting the perturbed microbiome is a novel therapeutic modality with the potential to decrease ARO colonization and infection and combat AMR without additional pressure for selection of further antimicrobial resistance. No trial has yet assessed the potential of a therapeutic microbial consortium for ARO decolonization and infection prevention after antibiotic treatment.
The investigational product, Microbial Ecosystem Therapeutic-2 (MET-2), is a defined microbial community derived from healthy donor stool. MET capsules are orally administered mixtures of bacterial strains cultured from the stool of a healthy donor. This study is designed to determine if a trial of administration of MET-2 after antibiotic treatment for bloodstream infections is feasible. Stool and plasma biomarkers to assess the effects of the intervention will also be evaluated.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 (≥18 years old) inpatient not admitted to the ICU or equivalent (step-up and step-down units are eligible)
- •Positive blood culture with an ARO:
- •AmpC beta-lactamase producing species: Enterobacter cloacae, Citrobacter spp., Klebsiella aerogenes, Serratia spp., Morganella morganii, Hafnia alvei OR
- •ESBL-producing gram-negative bacilli
- •Currently receiving treatment for the bloodstream infection
排除标准
- •Inability to swallow oral MET-2 or placebo capsule
- •Recipient of small bowel transplant
- •Inflammatory bowel disease, short bowel syndrome, diverting/non-diverting ileo/colostomy
- •Use of >3 days over-the-counter or prescription probiotics (not including food additives) within 10 days of enrolment
- •Receipt of fecal microbiota transplant (FMT) within 3 months of enrolment
- •Absolute neutrophil count <0.5x109/L
- •Death expected within 72 hours of enrolment
- •Planned continuation of non-prophylaxis antimicrobial therapy active against the bloodstream isolate for >42 days
- •Known pregnancy, planning to become pregnant during the study period, or breastfeeding
- •Any other reason in view of the site investigator or treating team
研究组 & 干预措施
MET-2
Participants randomized to the intervention will receive MET-2 daily for 10 days. MET-2 capsules are administered orally at 0.5 g per capsule, containing 3.1 x 10^5-10^11 colony forming units (CFU). An initial loading dose of 10 MET-2 capsules/day will be taken for 2 days (5 grams total). For the following 8 days, participants will take a maintenance dose of 3 MET-2 capsules/day (1.5 grams total).
干预措施: MET-2 (Drug)
Placebo
Participants randomized to the placebo will receive microcrystalline cellulose in a capsule, identical in appearance to MET-2 but not containing live bacteria. Participants will take the placebo in the same dosing schedule as the MET-2 arm: 10 capsules daily for 2 days, followed by 3 capsules daily for 8 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Adherence to MET-2/placebo for the treatment duration
时间窗: 30 days
Defined as \>80% of loading dose (16/20 pills) + \>75% of daily doses (18/24 pills) for the maintenance period, as determined by returned unused capsules
Recruitment rate overall and by study site
时间窗: 1.5 years
Defined by the numbers of eligible, consented, and randomized patients
次要结局
- Change in microbiome composition after intervention(180 days)
- Concentration of potential biomarkers in pre- and post-randomization blood and urine samples(180 days)
- Number of biomarker samples collected, by sample type and timepoint(30 days)