A Phase II Randomized Trial to Evaluate the Impact of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products on Recipient and Environmental Colonization With Multidrug-Resistant Organisms
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 6
- 主要终点
- Proportion of subjects with resolution of index MDRO colonization of the gut
研究概览
简要总结
This is a randomized, open label, comparative Phase II trial being conducted to determine whether fecal microbiota transplant using Penn Microbiome Therapy (PMT) products helps standard therapy eradicate antibiotic-resistant bacteria.
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
- •Multidrug-resistant organism (MDRO) infection of the bloodstream, respiratory tract, or urinary tract. Qualifying MDROs include extended-spectrum cephalosporin-resistant Enterobacterales (ESCRE) or carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa non-susceptible to two or more classes of antibiotics (MDR-PA), vancomycin-resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus aureus (MRSA).
- •On appropriate antibiotic treatment per clinical phenotypic susceptibility testing of the qualifying MDRO, and with a qualifying antibiotic class. Qualifying antibiotic classes include beta-lactam + beta-lactamase inhibitor, carbapenem (with or without betalactamase inhibitor), fluoroquinolone, lipopeptide, glycopeptide, or oxazolidinone.
- •Expected duration of inpatient antibiotic treatment for index MDRO infection at least 5 days total.
- •At least two calendar days remaining, and no more than 7 calendar days remaining prior to SCAIM (scheduled completion of inpatient appropriate antibiotics for the index MDRO infection).
- •Age ≥ 18 years.
排除标准
- •Evidence of colon/small bowel perforation at the time of study screening.
- •Unable to tolerate enteral and enema nutrition and medication administration (i.e., only able to tolerate intravenous nutrition and medications).
- •Goals of care are directed to comfort rather than curative measures.
- •Moderate or severe neutropenia within 10 calendar days prior to enrollment.
- •Known food allergy that could lead to anaphylaxis.
- •Known allergy to fecal microbiota transplant products or their components
- •Pregnancy or lactation
- •For subjects of childbearing potential (ages 18 to 55) and who are randomized to receive the intervention, the subject must have a negative pregnancy test within 24 hours prior to product administration
- •Female or male subjects (ages 18 to 55) of reproductive potential engaged in active sexual activity that could lead to a pregnancy must agree to use one of the following forms of birth control while receiving study medications and through day 28 following completion of treatment, at minimum:
- •i. Male or female condoms
- •ii. Diaphragm or cervical cap with spermicide, if available
- •iii. Intrauterine device (IUD)
- •iv. Oral contraceptives or other hormonal contraception
- •Known gastrointestinal disease that could affect the safety of fecal microbiota transplant at time of enrollment:
- •Inflammatory Bowel Disease (IBD)
- •Short Gut Syndrome
- •Bowel resection surgery
研究组 & 干预措施
ESCRE/CRE BL-BLI
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
干预措施: PMT (Drug)
ESCRE/CRE carbapenem +/- BLI
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI
干预措施: PMT (Drug)
ESCRE/CRE Fluoroquinolone
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone
干预措施: PMT (Drug)
MRSA lipo/glycopeptide
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide
干预措施: PMT (Drug)
MRSA oxazolidinone
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone
干预措施: PMT (Drug)
MDR-PA BL-BLI
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI)
干预措施: PMT (Drug)
MDR-PA carbapenem +/- BLI
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI
干预措施: PMT (Drug)
ESCRE/CRE carbapenem +/- BLI standard of care (SOC)
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
ESCRE/CRE BL-BLI standard of care (SOC)
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
ESCRE/CRE Fluoroquinolone standard of care (SOC)
MDRO: extended-spectrum cephalosporin resistant Enterobacterales ESCRE/CRE Antibiotic Class: Fluoroquinolone standard of care (SOC)
MRSA lipo/glycopeptide standard of care (SOC)
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: lipo/glycopeptide standard of care (SOC)
MRSA oxazolidinone standard of care (SOC)
MRDO: methicillin-resistant S. aureus (MRSA) Antibiotic Class: oxazolidinone standard of care (SOC)
MDR-PA BL-BLI standard of care (SOC)
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Beta Lactamase Inhibitors (BL-BLI) standard of care (SOC)
MDR-PA carbapenem +/- BLI standard of care (SOC)
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: carbapenem +/- BLI standard of care (SOC)
MDR-PA Fluoroquinolone standard of care (SOC)
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone standard of care (SOC)
VRE lipopeptide standard of care (SOC)
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide standard of care (SOC)
VRE oxazolidinone standard of care (SOC)
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone standard of care (SOC)
ESCRE/CRE cefepime/cefidericol standard of care (SOC)
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol standard of care (SOC)
MDR-PA cefepime/cefidericol standard of care (SOC)
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol standard of care (SOC)
MDR-PA Fluoroquinolone
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: Fluoroquinolone
干预措施: PMT (Drug)
VRE lipopeptide
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: lipopeptide
干预措施: PMT (Drug)
VRE oxazolidinone
MDRO: vancomycin resistant Enterococcus (VRE) Antibiotic Class: oxazolidinone
干预措施: PMT (Drug)
ESCRE/CRE cefepime/cefidericol
MDRO: ESCRE/CRE Antibiotic Class: cefepime/cefidericol
干预措施: PMT (Drug)
MDR-PA cefepime/cefidericol
MDRO: two-class non-susceptible Pseudomonas aeruginosa (MDR-PA) Antibiotic Class: cefepime/cefidericol
干预措施: PMT (Drug)
结局指标
主要结局
Proportion of subjects with resolution of index MDRO colonization of the gut
时间窗: 30 (+/-7)- day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
measured by selective stool culture, resolution will be defined as the absence of growth of the index MDRO on selective culture media.
Frequency of solicited adverse events (AEs)
时间窗: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Frequency of serious adverse events (SAEs)
时间窗: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Frequency of adverse events of special interest (AESIs)
时间窗: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
Frequency of medically attended adverse events (MAAEs)
时间窗: randomization until 180 day visit after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection)
次要结局
- Hospital admission(within 60 days of discharge from index hospitalization)
- Eradication of gut colonization with the index MDRO(7 days and 90 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Eradication of gut colonization with any of the included MDROs(7- , 30-, and 90-days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- All-cause mortality(30- and 60-days following SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Colectomy occurrence(within 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Cumulative days of hospitalization(from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Cumulative days of intensive care(from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Bacteria growth in blood samples(from randomization to 30 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Hospital admission(within 180 days after SCAIM (scheduled completion of appropriate inpatient antibiotics for the index MDRO infection))
- Instances of worsened abdominal pain, fever, tachycardia, and hypotension(randomization until 180-day visit)
- Instances of aspiration (including reduced oxygen saturation, tachypnea, or respiratory distress (PMT-002 upper entral delivery only)(randomization until 180-day visit)
- Instances of fever, diarrhea, nausea and vomiting(7-, 30-, 90- and 180 day follow up visits)
- Instances of new metabolic disease, including hyperglycemia, thyroid disease, weight gain or loss(30-, 90- and 180 day follow up visits)