A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patients With Gram-Negative Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 725
- 主要终点
- Number of Participants Surviving Through LFU Visit
研究概览
简要总结
To demonstrate that as adjunctive therapy to intravenous (IV) antibiotics, BAY 41-6551 400 mg (amikacin as free base) administered as an aerosol by the Pulmonary Drug Delivery System (PDDS) Clinical every 12 hours is safe and more effective than placebo (aerosolized normal saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and mechanically-ventilated patients with Gram-negative Pneumonia. The secondary endpoint objectives are to evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized placebo in pneumonia-related mortality, the Early Clinical Response at Day 10, the days on ventilation, and the days in the intensive care unit (ICU).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Males and non-pregnant, non-lactating females, 18 years of age or older
- •Intubated and mechanically-ventilated
- •Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph
- •Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory secretions, or suspected Gram-negative pathogen
- •Impaired oxygenation
- •Clinical Pulmonary Infection Score (CPIS) of at least 6
- •Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms
排除标准
- •History of hypersensitivity to amikacin or other aminoglycosides
- •Has received antibiotic therapy for Gram-negative pneumonia for greater than 48 hours at the time of randomization
- •Known or suspected bacteremia secondary to Staphylococcus aureus
- •A positive urine and/or serum beta-human Chorionic Gonadotropin pregnancy test
- •Patients with a serum creatinine > 2 mg/dL (177 µmol/L) [Exception: Patients with a serum creatinine > 2 mg/dL (177 µmol/L) and being treated with continuous renal replacement therapy (Continuous Veno-Venous Hemodialysis and CVVHemoDiafiltration) or daily hemodialysis will receive the aerosol study drug treatment]
- •Has been on mechanical ventilation for > 28 days
- •Is participating in or has participated in other investigational interventional studies within the last 28 days prior to study treatment
- •The risk of rapidly fatal illness and death within 72 hrs, or any concomitant condition not related to ventilator-associated pneumonia that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy
- •Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10
- •Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)
研究组 & 干预措施
Amikacin inhale (BAY41-6551)
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
干预措施: Amikacin Inhalation Solution (BAY41-6551) (Drug)
Placebo
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
干预措施: Aerosolized Placebo (Drug)
结局指标
主要结局
Number of Participants Surviving Through LFU Visit
时间窗: Up to 28-32 days after start of study treatment
The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival.
次要结局
- Number of Participants With Early Clinical Response(Up to 10 days after start of study treatment)
- Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit(Up to 28-32 days after start of study treatment)
- Number of Days on Mechanical Ventilation Through LFU Visit(Up to 28-32 days after start of study treatment)
- Number of Days in the ICU Through LFU Visit(Up to 28-32 days after start of study treatment)