A Randomized, Open-Label, Multicenter Study to Assess the Safety and Tolerability of Doripenem Compared With Imipenem in the Treatment of Subjects With Complicated Intra-Abdominal Infections or Ventilator Associated Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 146
- 主要终点
- Patients With Incidence of Treatment-emergent Adverse Events (TEAEs).
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of doripenem compared to imipenem in Ventilator-assisted pneumonia and complicated Intra-abdominal Infection. The study population will include hospitalized patients (or patients resident in a chronic health care facility) who have a diagnosis of either Ventilator associated pneumonia or complicated Intra-abdominal Infection.
详细描述
This is a randomized (study drug assigned by chance), open-label (all people involved know the identity of the intervention), multicenter study that will evaluate the safety and tolerability of doripenem (an antibiotic used to treat infections) in patients with ventilator-associated pneumonia (VAP) or complicated intra-abdominal infection (cIAI). Approximately 250 patients will be assigned in a 3:1 ratio to receive doripenem or imipenem/cilastatin (188 patients randomized to receive doripenem and 62 patients randomized to receive imipenem/cilastatin). Furthermore, patients who receive doripenem or imipenem/cilastatin will be stratified by disease (VAP or cIAI). Therefore, for reporting purposes, there will be 4 groups: Patients with VAP treated with doripenem, patients with VAP treated with imipenem/cilastatin, patients with cIAI treated with doripenem, and patients with cIAI treated with imipenem/cilastatin. Study drug will be administered intravenously (iv) (through a vein) for 7 to 14 days for patients with VAP and for 5 to 14 days for patients with cIAI. The maximum duration of study drug is 14 days. Vancomycin and/or amikacin may be added to the study drug regimen as adjunctive therapy for those patients who meet study specified criteria. The recommended dosage of vancomycin is 1 g every 12 hours administered by iv infusion. The addition of amikacin is at the discretion of the investigator for patients with VAP (not cIAI) and the recommended dosing regimen for amikacin is 15 mg/kg given iv once a day. Alternative amikacin regimens or other aminoglycoside regimens may be permitted. Safety will be assessed during the study by the monitoring of adverse events, evaluation of laboratory test results, and changes in vital signs. The primary endpoint of this study is to assess the overall incidence of treatment-emergent adverse events (TEAEs) from the initiation of the first infusion of study drug and up to 30 days after the completion of study drug therapy. Treatment-emergent adverse events are defined as adverse events that occur or worsen between the initial infusion of study drug up to 30 days after the last dose of study drug. The hypothesis for this study is that doripenem has a similar safety profile to imipenem. Doripenem (1g at 8-hour intervals over a period of 4 hours) or imipenem/cilastatin (1g at 8-hours over a period of 1 hour) will be administered by intravenous (iv) infusion (delivery of drug slowly into the vein over a period of time). Patients diagnosed with ventilator associated pneumonia (VAP) will be treated for 7 to 14 days and patients with complicated intra-abdominal infections (cIAI) will be treated for 5 to 14 days.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be hospitalized with a diagnosis of Ventilator-Assisted Pneumonia (VAP) or complicated Intra-Abdominal Infection (cIAI)
- •Patients with VAP must have been hospitalized (or been in a chronic care facility) for >= 5 days, have received mechanical ventilation for >= 48 hours, have a Clinical Pulmonary Infection Score (CPIS) of >= 5, have new or progressive radiographic infiltrates (not related to another disease process)
- •Patients with cIAI must have clinical evidence of intra-abdominal infection, abdominal pain or tenderness, localized or diffuse abdominal wall rigidity, mass, ileus or have a requirement for surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of study entry
排除标准
- •Patients with a history of acute hepatic failure or acute decompensation of chronic hepatic failure, history of severe impairment of renal function, history of immunocompromising illness, acquired immunodeficiency syndrome (AIDS), or human immunodeficiency virus (HIV) with a CD4 count less than 200 cells/mL within the past 6 months
- •organ (including bone marrow) transplant recipients
- •hematologic malignancy
- •use of immunosuppressive therapy at screening, including use of high dose corticosteroids (e.g., > 40 mg prednisone or equivalent per day for > 2 weeks)
- •history of any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure and septic shock)
研究组 & 干预措施
001
Doripenem 1 gram infused over 4 hours at 8-hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion
干预措施: Doripenem (Drug)
002
Imipenem/cilastatin 1 gram infused over 1 hour at 8 hour intervals for patients with Ventilator-Associated Pneumonia (VAP) for 7 to 14 days Vancomycin and/or amikacin may be added as adjunctive therapy as per investigator discretion
干预措施: Imipenem/cilastatin (Drug)
003
Doripenem 1 gram infused over 4 hours at 8 hour intervals for patients with complicated intrabdominal infections (cIAI) for 5 to 14 days Vancomycin may be added as adjunctive therapy as per investigator discretion
干预措施: Doripenem (Drug)
004
Imipenem/cilastatin 1 gram infused over 1 hour at 8 hour intervals for patients with complicated intrabdominal infections (cIAI) for 5 to 14 days Vancomycin may be added as adjunctive therapy as per investigator discretion
干预措施: Imipenem/cilastatin (Drug)
结局指标
主要结局
Patients With Incidence of Treatment-emergent Adverse Events (TEAEs).
时间窗: from the initiation of the first infusion of study drug therapy and up to 30 days after the completion of study drug therapy
Treatment-emergent adverse events (TEAEs) are defined as AEs with onset dates on or after the date of the start of the infusion of first dose of study therapy and within 30 days after administration of the last dose of study therapy.
次要结局
- Patients With cIAI Who Were Clinically Cured(7 to 14 days after the end of IV therapy)
- Patients With VAP Who Were Clinically Cured(7 to 14 days after the end of IV therapy)