A Pilot Study of Ceftolozane-Tazobactam in Conjunction With Rapid Molecular Diagnosis for Directed Treatment of Pseudomonas Aeruginosa Bacteremia and Pneumonia in Patients With Hematological Malignancies and Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Global response at end of therapy
研究概览
简要总结
The goal of this clinical trial is to learn whether the antibiotic ceftolozane-tazobactam works to treat serious Pseudomonas aeruginosa infections in people with blood cancers or who received a stem cell transplant. The main question it aims to answer is whether participants reach clinical success 30 days after the infection is first found. Clinical success means the person is alive, their infection symptoms are improving, and the infection has not returned.
Participants will receive ceftolozane-tazobactam through a vein every 8 hours for 10 to 14 days. Treatment may continue for up to 21 days if the infection is not improving or keeps coming back. The infection is diagnosed using the hospital's standard rapid molecular tests, which help confirm Pseudomonas aeruginosa quickly so treatment can begin right away.
Researchers will follow participants during their hospital stay and check on them around 30 and 60 days to see how well the treatment worked. The study will also look at how long it takes for the infection to clear, how long participants stay in the hospital or intensive care unit, and whether the bacteria become resistant to antibiotics.
In addition to the prospective ceftolozane-tazobactam group, the study includes a historical control group made up of patients with similar infections who were treated in the past with standard anti-pseudomonal antibiotics (such as cefepime, ceftazidime, piperacillin-tazobactam, or meropenem). Data from these historical controls are collected by chart review and analyzed alongside the prospective group to compare outcomes. Historical controls do not receive study-directed treatment and are not actively enrolled under this protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study. No parties are masked.
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
- •Eligibility Criteria
- •Inclusion Criteria
- •Presence of a hematologic malignancy or a history of hematopoietic stem cell transplantation
- •Identification of Pseudomonas aeruginosa by rapid molecular diagnostic testing from a positive blood culture or from a respiratory sample in the setting of radiologically documented pneumonia with compatible clinical symptoms
- •Age 18 years or older
- •Ability of the participant or legally authorized representative to provide informed consent
排除标准
- •Receipt of more than 72 hours of non-study anti pseudomonal therapy for the infection being treated
- •Known anaphylactic hypersensitivity or allergic reaction to cephalosporins
- •History of a Pseudomonas aeruginosa isolate with a ceftolozane or tazobactam MIC greater than 4 micrograms per milliliter
- •Polymicrobial aerobic Gram negative infection, as determined by the infectious diseases research team
- •Hemodialysis, continuous renal replacement therapy, or creatinine clearance less than 15 milliliters per minute
- •Expected mortality within 48 hours of screening
- •Eligibility Criteria for Historical Controls
- •Inclusion Criteria
- •Presence of a hematologic malignancy or a history of hematopoietic stem cell transplantation
- •Identification of Pseudomonas aeruginosa associated with bacteremia and or pneumonia
- •Age 18 years or older
- •Survival greater than 48 hours after initiation of anti pseudomonal therapy for Pseudomonas aeruginosa bacteremia and or pneumonia
- •Exclusion Criteria
- •Known anaphylactic hypersensitivity or allergic reaction to cephalosporins
- •History of a Pseudomonas aeruginosa isolate with a ceftolozane or tazobactam MIC greater than 4 micrograms per milliliter
- •Polymicrobial aerobic Gram negative infection, as determined by the infectious diseases research team
- •Hemodialysis, continuous renal replacement therapy, or creatinine clearance less than 15 milliliters per minute
研究组 & 干预措施
Ceftolozane-Tazobactam
Participants receive ceftolozane-tazobactam by injection directly into the vein (intravenously, IV) every 8 hours for 10-14 days.
干预措施: Ceftolozane / Tazobactam Injection (Drug)
结局指标
主要结局
Global response at end of therapy
时间窗: Day 60
The proportion of subjects with a complete or partial Global Response (GR). Complete response is defined as "Survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease and radiological abnormalities, and microbiological evidence of eradication of disease." Partial response is defined as "Survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease and radiological abnormalities, and evidence of clearance of cultures."
次要结局
- Survival at 60 days(Day 60)
- Time in days to resolution of bacteremia(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28)
- Time in days until stabilization or resolution of pneumonic infiltrates(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28)
- Time in days of ICU stays(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60)
- Time in days to appropriate therapy(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60)
- Incidence of abnormal and physical examinations findings - neurological(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - heart/cardiovascular(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Time in days to initial antimicrobial therapy(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60)
- Change in days until emergence of other bacteria(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28)
- Number of days on ventilator, as measured by assessment of clinical status(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28)
- Time in days to emergence of resistant isolates(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28)
- Survival at 30 days(Day 30)
- Time in days of hospital stays(Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28, Day 30, Day 60)
- Change of microbiological eradication(Screen, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14, Day 15, Day 16, Day 17, Day 18, Day 19, Day 20, Day 21, Day 22, Day 23, Day 24, Day 25, Day 26, Day 27, Day 28)
- Incidence of abnormal and physical examinations findings - general appearance(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - lungs(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - abdomen(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - endocrine(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - extremities(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - lymphatic(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))
- Incidence of abnormal and physical examinations findings - skin(3 times weekly through treatment (Week 1, Week 2, Week 3, Week 4))