NCT02321800已完成2 期
A Multicenter, Double-blind, Randomized, Clinical Study to Assess the Efficacy and Safety of Intravenous S-649266 in Complicated Urinary Tract Infections With or Without Pyelonephritis or Acute Uncomplicated Pyelonephritis Caused by Gram-Negative Pathogens in Hospitalized Adults in Comparison With Intravenous Imipenem/Cilastatin
Shionogi0 个研究点目标入组 452 人开始时间: 2015年2月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 452
- 主要终点
- Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure
研究概览
简要总结
The purpose of this study was to determine the efficacy and safety of intravenous cefiderocol (S-649266) in hospitalized adults with complicated urinary tract infections caused by Gram-negative pathogens.
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
- •Hospitalized male and female patients ≥ 18 years
- •Clinical diagnosis of either complicated urinary tract infections (cUTI) with or without pyelonephritis or acute uncomplicated pyelonephritis
- •cUTI diagnosed with a history of ≥ 1 of the following:
- •Indwelling urinary catheter or recent instrumentation of the urinary tract
- •Urinary retention (caused by benign prostatic hypertrophy)
- •Urinary retention of at least 100 mL or more of residual urine after voiding (neurogenic bladder)
- •Obstructive uropathy
- •Azotemia caused by intrinsic renal disease (blood urea nitrogen and creatinine values greater than normal laboratory values) OR Pyelonephritis and normal urinary tract anatomy, ie, acute uncomplicated pyelonephritis AND
- •At least 2 of the following signs or symptoms:
- •Chills or rigors or warmth associated with fever (temperature greater than or equal to 38 degrees Celsius)
- •Flank pain (pyelonephritis) or suprapubic/pelvic pain (cUTI)
- •Nausea or vomiting
- •Dysuria, urinary frequency, or urinary urgency
- •Costo-vertebral angle tenderness on physical examination AND
- •All subjects had to have urinalysis evidence of pyuria demonstrated by 1 of the following:
- •Dipstick analysis positive for leukocyte esterase
- •≥ 10 white blood cells (WBCs) per μL in unspun urine, or ≥ 10 WBCs per high power field in spun urine
- •Positive urine culture within 48 hours prior to randomization containing ≥10^5 colony forming unit (CFU)/mL of a Gram-negative uropathogen likely to be susceptible to imipenem (IPM)
- •Patients who were treated previously with an empiric antibiotic other than the study drugs but failed treatment, both clinically and microbiologically, were eligible for the study if they had an identified Gram-negative uropathogen that was not susceptible to the previously used empiric treatment and likely to be susceptible to IPM
- •Subjects receiving antibiotic prophylaxis for UTI who present with signs and symptoms consistent with an active new UTI
排除标准
- •Urine culture identifies only a Gram-positive pathogen and/or a Gram-negative uropathogen resistant to IPM
- •Urine culture at study entry isolates more than 2 uropathogens or patient has a confirmed fungal UTI
- •Asymptomatic bacteriuria, the presence of >10^5 CFU/mL of a uropathogen and pyuria but without local or systemic symptoms
- •Patient is receiving hemodialysis or peritoneal dialysis
研究组 & 干预措施
Cefiderocol
Experimental
Participants received 2 g cefiderocol by intravenous injection once every 8 hours for 7 to 14 days.
干预措施: Cefiderocol (Drug)
Imipenem/cilastatin
Active Comparator
Participants received 1 g each of imipenem/cilastatin by intravenous injection once every 8 hours for 7 to 14 days.
干预措施: Imipenem/cilastatin (Drug)
结局指标
主要结局
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure
时间窗: Test of cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14 to 21)
The primary efficacy endpoint was the composite outcome of clinical response and microbiological response at the test of cure assessment, defined as 7 days (±2 days) after the end of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at \> 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
次要结局
- Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment(Early assessment (EA; Day 4))
- Percentage of Participants With Microbiological Eradication at Early Assessment(Early assessment, Day 4)
- Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment(End of treatment (EOT; Day 7 to 14))
- Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up(Follow-up (FUP; 14 days after end of treatment, Day 21 to 28))
- Percentage of Participants With Microbiological Eradication at Follow-up(Follow-up, 14 days after end of treatment, Day 21 to 28)
- Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen(End of treatment, Day 7 to 14)
- Percentage of Participants With Microbiological Eradication at Test of Cure(Test of cure (7 days after end of treatment, Day 14 to 21))
- Percentage of Participants With Microbiological Eradication at End of Treatment(End of treatment, Day 7 to 14)
- Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen(Early assessment, Day 4)
- Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen(Test of cure; 7 days after end of treatment, Day 14 to 21)
- Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen(Follow-up, 14 days after the end of treatment, Day 21 to 28)
- Percentage of Participants With Clinical Response at Test of Cure(Test of cure, 7 days after end of treatment, Day 14 to 21)
- Percentage of Participants With Clinical Response at End of Treatment(End of treatment, Day 7 to 14)
- Percentage of Participants With Clinical Response at Follow-up(Follow-up, 14 days after end of treatment, Day 21 to 28)
- Percentage of Participants With Clinical Response at Early Assessment(Early assessment, Day 4)
- Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen(Test of cure, 7 days after end of treatment, Day 14 to 21)
- Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen(Early assessment, Day 4)
- Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen(End of treatment, Day 7 to 14)
- Percentage of Participants With Clinical Response at Follow-up Per Uropathogen(Follow-up, 14 days after the end of treatment, Day 21 to 28)
- Plasma Concentration of Cefiderocol(On Day 3 of dosing prior to infusion, end of infusion, and at 1 hour post infusion)
- Urine Concentration of Cefiderocol(Day 3, 2 hours and 6 hours after end of infusion)
- Number of Participants With Adverse Events(From first dose of study drug until 28 days after end of treatment; Day 35 to 42)
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