A Randomized, Active-controlled Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 207
- 试验地点
- 4
- 主要终点
- Proportion of Patients With Nephrotoxicity
研究概览
简要总结
This is a 2-part study, with Part A being the randomized, controlled portion of the study in patients with ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or bacteremia. Part B is the single-group portion of the study and includes ABC infections that are resistant to or have failed colistin or polymyxin B treatment, as detailed in the inclusion criteria.
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
盲法说明
Study drugs will not be masked due to logistical reasons, every attempt will be made to maintain the blind for patients, all staff at the site, and the Sponsor or its designees, except for the treatment physician and other immediate healthcare providers.
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
- •A confirmed diagnosis of a serious infection that will require treatment with IV antibiotics;
- •A known infection caused by ABC (bacteremia, HABP, VABP, VP, cUTI or AP, or surgical or post-traumatic wound infections) as either a single pathogen or member of a polymicrobial infection based on evidence from culture or, if available, rapid diagnostic test from a sample collected within 72 hours prior to randomization (HABP/VABP/VP patients), AND 1 of the following:
- •Has received no more than 48 hrs of potentially effective (ie, Gram negative coverage) antimicrobial therapy prior to the first dose of study drug;
- •Is clinically failing prior treatment regimens
- •APACHE II score 10 and 30 inclusive, or SOFA score between 7 and 11 inclusive, at time of diagnosis
- •Expectation, in the judgment of the Investigator, that the patient will benefit from effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study
- •Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method of contraception (ie, condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last dose of study drug.
- •Has an infection (HABP, VABP, VP, bacteremia, cUTI, AP, or surgical or post-traumatic wound infections) caused by ABC organisms known to be resistant to colistin (defined as MIC ≥4 mg/L by a non-agar based method);
- •Known to be resistant to colistin or polymyxin B; or
- •Known intolerance to colistin; or
- •Has myasthenia gravis or another neuromuscular syndrome(s) that contraindicates colistin and is not ventilated; or
- •Has acute kidney injury and is receiving renal replacement therapy at study entry.
排除标准
- •Evidence of active concurrent pneumonia requiring additional antimicrobial treatment
- •Presence of suspected or confirmed deep seated bacterial infections such as bacterial Gram negative osteomyelitis, endocarditis, or meningitis requiring prolonged therapy, as determined by history and/or physical examination;
- •Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 60 mmHg;
- •Pregnant or breastfeeding women;
- •Receiving peritoneal dialysis;
- •Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study;
- •Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy;
研究组 & 干预措施
Part A - Group 1
Part A was the pivotal, assessor-blind, randomized, comparative portion of the study in patients with documented ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia.
Part A - Group 1 (experimental): 1.0 g sulbactam/1.0 g durlobactam IV infused over 3 hours every 6 hours (q6h) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h
干预措施: Sulbactam (Drug)
Part A - Group 1
Part A was the pivotal, assessor-blind, randomized, comparative portion of the study in patients with documented ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia.
Part A - Group 1 (experimental): 1.0 g sulbactam/1.0 g durlobactam IV infused over 3 hours every 6 hours (q6h) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h
干预措施: Durlobactam (Drug)
Part A - Group 1
Part A was the pivotal, assessor-blind, randomized, comparative portion of the study in patients with documented ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), ventilated pneumonia (VP), or bacteremia.
Part A - Group 1 (experimental): 1.0 g sulbactam/1.0 g durlobactam IV infused over 3 hours every 6 hours (q6h) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h
干预措施: Imipenem/Cilastatin 500 mg/500 mg (Drug)
Part A - Group 2
Part A - Group 2 (control group): 2.5 mg/kg colistin IV infused over 30 minutes every 12 hours (after an initial loading dose of colistin 2.5 to 5 mg/kg) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
干预措施: Colistin (Drug)
Part A - Group 2
Part A - Group 2 (control group): 2.5 mg/kg colistin IV infused over 30 minutes every 12 hours (after an initial loading dose of colistin 2.5 to 5 mg/kg) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
干预措施: Imipenem/Cilastatin 500 mg/500 mg (Drug)
Part B - Group 3
Part B (Group 3) was the open-label, supportive portion of the study that included patients known to have HABP, VABP, VP, and/or bacteremia infections associated with ABC organisms resistant to colistin or polymyxin B, who failed a colistin or polymyxin B regimen prior to study entry or were on acute renal replacement therapy, and patients with infections due to colistin- or polymyxin B-resistant ABC with sources of infection other than HABP, VABP, VP, and/or bacteremia.
Part B - Group 3: 1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
干预措施: Sulbactam (Drug)
Part B - Group 3
Part B (Group 3) was the open-label, supportive portion of the study that included patients known to have HABP, VABP, VP, and/or bacteremia infections associated with ABC organisms resistant to colistin or polymyxin B, who failed a colistin or polymyxin B regimen prior to study entry or were on acute renal replacement therapy, and patients with infections due to colistin- or polymyxin B-resistant ABC with sources of infection other than HABP, VABP, VP, and/or bacteremia.
Part B - Group 3: 1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
干预措施: Durlobactam (Drug)
Part B - Group 3
Part B (Group 3) was the open-label, supportive portion of the study that included patients known to have HABP, VABP, VP, and/or bacteremia infections associated with ABC organisms resistant to colistin or polymyxin B, who failed a colistin or polymyxin B regimen prior to study entry or were on acute renal replacement therapy, and patients with infections due to colistin- or polymyxin B-resistant ABC with sources of infection other than HABP, VABP, VP, and/or bacteremia.
Part B - Group 3: 1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
干预措施: Imipenem/Cilastatin 500 mg/500 mg (Drug)
结局指标
主要结局
Proportion of Patients With Nephrotoxicity
时间窗: 28 days
The primary safety endpoint for the study is nephrotoxicity, as measured by the Risk-Injury-Failure-Loss-End-stage renal disease (RIFLE) criteria, in the MITT population in Part A.
Proportion of Patients With All-Cause Mortality in CRABC m-MITT Population
时间窗: 28 Days
The primary efficacy endpoint for the study is 28-day all-cause mortality in the CRABC m-MITT population in Part A.
次要结局
未报告次要终点