A PROSPECTIVE, RANDOMIZED,OPEN-LABEL, COMPARATIVE STUDY TO ASSESS THE EFFICACY, SAFETY AND TOLERABILITY OF AZTREONAM- AVIBACTAM (ATM-AVI) AND BEST AVAILABLE THERAPY FOR THE TREATMENT OF SERIOUS INFECTIONS DUE TO MULTI-DRUG RESISTANT GRAM- NEGATIVE BACTERIA PRODUCING METALLO -Β-LACTAMASE (MBL)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 15
- 试验地点
- 41
- 主要终点
- Percentage of Participants With Clinical Cure at the Test of Cure (TOC) Visit -Microbiological Intent to Treat (Micro-ITT) Analysis Set
研究概览
简要总结
Phase 3 study to determine the efficacy, safety, and tolerability of aztreonam- avibactam (ATM- AVI) versus best available therapy (BAT) in the treatment of hospitalized adults with complicated intra-abdominal infections (cIAI), nosocomial pneumonia (NP) including hospital acquired pneumonia (HAP) and ventilator associated pneumonia (VAP), complicated urinary tract infections (cUTI), or bloodstream infections (BSI) due to metallo-β-lactamase (MBL)- producing Gram-negative bacteria.
详细描述
This is a prospective, randomized, multicenter, open-label, parallel group, comparative study to determine the efficacy, safety, and tolerability of aztreonam- avibactam (ATM- AVI) versus best available therapy (BAT) in the treatment of hospitalized adults with complicated intra-abdominal infections (cIAI), nosocomial pneumonia (NP) including hospital acquired pneumonia (HAP) and ventilator associated pneumonia (VAP), complicated urinary tract infections (cUTI), or bloodstream infections (BSI) due to metallo-β-lactamase (MBL)- producing Gram-negative bacteria.
The study will randomize approximately 60 subjects in a 2:1 randomization scheme (ATM-AVI: BAT) with infections due to MBL-producing Gram-negative bacteria. Molecular testing at the central microbiology laboratory will be performed to confirm the MBL status of the organism upon study completion or at pre-designated intervals.
The study will consist of a Screening Visit (Visit 1), a Baseline visit (Visit 2) on Day 1 of the study treatment, ongoing treatment visits (Visits 3 to 15) from Day 2 to Day 14, an End of Treatment (EOT) visit (Visit 16) within 24 hours after the last infusion, a Test of Cure (TOC) visit (Visit 17) on Day 28 (±3 days) and a Late Follow Up (LFU) visit (Visit 18) on Day 45 (±3 days).
Subjects will be stratified at randomization based on infection type (cIAI, HAP/VAP, cUTI or BSI). The number of subjects with cUTI will be no more than approximately 75% of the study population.
After obtaining written informed consent and confirming eligibility, subjects will be randomized in a 2:1 ratio to the ATM AVI treatment arm or the BAT treatment arm according to a central randomization schedule (approximately 40 (ATM AVI) and approximately 20 (BAT) subjects per group).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ATM- AVI Aztreonam- Avibactam (ATM-AVI) Active Treatment Arm
干预措施: ATM-AVI (Combination Product)
Best Available Therapy (BAT) Comparator Treatment Arm
干预措施: BAT (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Cure at the Test of Cure (TOC) Visit -Microbiological Intent to Treat (Micro-ITT) Analysis Set
时间窗: Day 28
Clinical cure was defined as improvement in baseline signs and symptoms such that no further antimicrobial treatment was required for the index infection (i.e., cIAI, cUTI, HAP/VAP or BSI) after study treatment. Also for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. The clinical response assessment was determined by a blinded independent adjudication committee. 95% confidence interval (CI) was calculated using Jeffrey's method.
次要结局
- Percentage of Participants With Clinical Cure at the EOT Visit- ME Analysis Set(Up to 24 hours after the last infusion on Day 14)
- Percentage of Participants With a Favorable Per Participant Microbiological Response at TOC Visit-Micro-ITT Analysis Set(Day 28)
- Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the TOC Visit-ME Analysis Set(Day 28)
- Percentage of Participants With a Favorable Per Participant Microbiological Response at EOT Visit-ME Analysis Set(Up to 24 hours after the last infusion on Day 14)
- Percentage of Participants Who Died Within 28 Days From Randomization- Micro ITT Analysis Set(From randomization up to Day 28)
- Number of Participants With Abnormal Physical Examination Findings(Baseline (last non-missing value observed before start of treatment on Day 1), EOT (Up to 24 hours after the last infusion on Day 14), TOC (Day 28))
- Percentage of Participants With Clinical Cure at the TOC Visit-Microbiologically Evaluable (ME) Analysis Set(Day 28)
- Percentage of Participants With Clinical Cure at the End of Treatment (EOT) Visit- Micro-ITT Analysis Set(Up to 24 hours after the last infusion on Day 14)
- Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the EOT Visit-ME Analysis Set(Up to 24 hours after the last infusion on Day 14)
- Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events(From first dose of study treatment (Day 1) until late follow-up visit (Up to Day 45))
- Percentage of Participants With a Favorable Per Participant Microbiological Response at EOT Visit-Micro-ITT Analysis Set(Up to 24 hours after the last infusion on Day 14)
- Percentage of Participants With a Favorable Per Participant Microbiological Response at TOC Visit-ME Analysis Set(Day 28)
- Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the EOT Visit-Micro-ITT Analysis Set(Up to 24 hours after the last infusion on Day 14)
- Percentage of Pathogens According to Favourable Per-Pathogen Microbiological Response at the TOC Visit-Micro-ITT Analysis Set(Day 28)
- Percentage of Participants Who Died Within 28 Days From Randomization-ITT Analysis Set(From randomization up to Day 28)
- Number of Participants With Vital Sign Abnormalities(From first dose of study treatment (Day 1) until TOC (Up to Day 28))
- Number of Participants With Clinically Significant Abnormalities in Hematology Assessments(From first dose of study treatment (Day 1) until TOC (Up to Day 28))
- Number of Participants With Clinically Significant Abnormalities in Clinical Chemistry Assessments(From first dose of study treatment (Day 1) until TOC (Up to Day 28))
- Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)(From first dose of study treatment (Day 1) until TOC (Up to Day 28))