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临床试验/CTRI/2018/09/015762
CTRI/2018/09/015762已完成3 期

A PHASE 3 PROSPECTIVE, RANDOMIZED, MULTICENTER, OPEN-LABEL, CENTRAL ASSESSOR-BLINDED, PARALLEL GROUP, COMPARATIVE STUDY TO DETERMINE THE EFFICACY, SAFETY AND TOLERABILITY OFAZTREONAM-AVIBACTAM (ATM-AVI) ± METRONIDAZOLE (MTZ) VERSUS MEROPENEM ± COLISTIN (MER±COL) FOR THE TREATMENT OF SERIOUS INFECTIONS DUE TO GRAM-NEGATIVE BACTERIA, INCLUDINGMETALLO-Β-LACTAMASE (MBL) – PRODUCING MULTIDRUG RESISTANT PATHOGENS, FOR WHICH THERE ARE LIMITED OR NO TREATMENT OPTIONS

Pfizer Limited13 个研究点 分布在 1 个国家目标入组 425 人开始时间: 2021年8月29日最近更新:
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试验速览

阶段
3 期
状态
已完成
入组人数
425
试验地点
13
主要终点
proportion of subjects with clinical cure in the ITT and CE analysis sets
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

A Phase 3 comparative study to determine theefficacy, safety and tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole(MTZ) versus Meropenem (MER) ± Colistin (COL) for the treatment of seriousinfections due to Gram negative bacteria.

研究设计

研究类型
Interventional
分配方式
Computer generated randomization
盲法
Open Label

入排标准

年龄范围
18.00 Year(s) 至 99.00 Year(s)（—）
性别
All

入选标准

  • •Inclusion Criteria: All subjects:
  • •Male or female from 18 years of age
  • •Provision of informed consent
  • •Confirmed diagnosis of HAP/VAP or cIAI requiring iv antibiotic treatment
  • •Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met and negative pregnancy test Additional for cIAI:
  • •Diagnosis of cIAI, EITHER: Intra-operative/postoperative enrolment with visual confirmation of cIAI.
  • •OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry
  • •Surgical intervention within 24 hours (before or after) the administration of the first dose of study drug Additional for HAP/VAP:
  • •Onset symptoms > 48h after admission to or <7 days after discharge from an inpatient care facility
  • •New or worsening infiltrate on CXR or CT scan
  • •Clinical signs and symptoms and laboratory findings consistent with HAP/VAP
  • •Respiratory specimen obtained for Gram stain and culture following onset of symptoms and prior to randomisation.

排除标准

  • •All subjects:
  • •APACHE II score > 30
  • •Confirmed or suspected infection caused by Gram-negative species not expected to respond to study drug, or Gram-positive species
  • •Receipt of >24 hr systemic antibiotic within 48h prior to randomisation (exception in case of treatment failure)
  • •History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem, monobactam or other ß-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
  • •Known Clostridium difficle associated diarrhoea
  • •Requirement for effective concomitant systemic antibacterials or antifungals
  • •Creatinine clearance is equals to 15 ml per min or requirement or expectation for renal replacement therapy
  • •Acute hepatitis, cirrhosis, acute hepatic failure, chronic hepatic failure
  • •Hepatic disease as indicated by AST or ALT greater than 3 X ULN.
  • •Patients with AST and or or ALT up to 5 X ULN are eligible if acute and documented by the investigator as being directly related infectious process
  • •Patient has a total bilirubin greater than 2 X ULN unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilberts disease.
  • •ALP greater than 3 X ULN.
  • •Patients with values greater than 3 X ULN and Less than 5 X ULN are eligible if acute and directly related to the infectious process being treated
  • •Absolute neutrophil count less than 500 per mm
  • •Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
  • •Any other condition that may confound the results of the study or pose additional risks to the subject
  • •Unlikely to comply with protocol
  • •History of epilepsy or seizure disorders excluding febrile seizures of childhood Additional for cIAI
  • •Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery < 24 h
  • •Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess
  • •Staged abdominal repair (STAR), open abdomen technique or marsupialisation Additional for HAP/VAP
  • •APACHE II score < 10
  • •Known or high likelihood of Gram-positive monomicrobial infection
  • •Lung abscess, pleural empyema, post-obstructive pneumonia
  • •Lung or heart transplant
  • •Myasthenia gravis.

结局指标

主要结局

proportion of subjects with clinical cure in the ITT and CE analysis sets

时间窗: Test of Cure (TOC) visit, Day 28 ± 3 days

次要结局

  • PK of AVI(Days 1 and 4)
  • PK/PD relationship between exposure and clinical response for ATM AVI±MTZ in the popPK analysis set(Test of Cure (TOC) visit, Day 28 ± 3 days)
  • Proportion of subjects who died(Day 28)
  • Proportion of subjects with a favorable per subject microbiological response in the micro ITT and ME analysis sets(Test of Cure (TOC) visit, Day 28± 3 days)
  • Proportion of subjects with clinical cure by infection type in the ITT and CE analysis sets(Test of Cure (TOC) visit, Day 28± 3 days)
  • Proportion of subjects with clinical cure for subjects with MBL positive pathogens in the micro ITT and ME analysis sets.(Test of Cure (TOC) visit, Day 28± 3 days)
  • Description of safety in terms of adverse events(Throughout study to Late Follow Up visit (Day 45 ± 3 days))
  • PK of ATM(Days 1 and 4)
  • Proportion of subjects with clinical cure in the m-ITT and ME analysis sets(Test of Cure (TOC) visit, Day 28± 3 days)
  • PK/PD relationship between exposure and microbiological response for ATM/AVI±MTZ in the popPK analysis set(Test of Cure (TOC) visit, Day 28± 3 days)
  • PK/PD relationship between exposure and clinical response for ATM/AVI ± MTZ in the popPK analysis set(Test of Cure (TOC) visit, Day 28 ± 3 days)

研究者

申办方类型
Pharmaceutical industry-Global

研究点 (13)

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