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临床试验/NCT01595438
NCT01595438已完成3 期

A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Pfizer1 个研究点 分布在 1 个国家目标入组 598 人开始时间: 2012年10月最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
发起方
Pfizer
入组人数
598
试验地点
1
主要终点
Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test
研究概览研究设计入排标准研究组 & 干预措施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

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis

详细描述

A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

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 90 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •18 to 90 years of age inclusive
  • •Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
  • •Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
  • •Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis.

排除标准

  • •Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
  • •Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
  • •Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
  • •Patient is immunocompromised
  • •Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality

研究组 & 干预措施

Ceftazidime - Avibactam ( CAZ-AVI)

Experimental

IV treatment

干预措施: Ceftazidime - Avibactam ( CAZ-AVI) (Drug)

Doripenem

Active Comparator

IV treatment

干预措施: Doripenem (Drug)

结局指标

主要结局

Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test

时间窗: At Day 5 visit. Day 5 visit is based on 24 hour periods from the first dose date and time.

Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).

Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test

时间窗: At TOC visit. TOC visit is 21 to 25 days from Randomization.

Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).

Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test

时间窗: At TOC visit. TOC visit is 21 to 25 days from Randomization.

Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.

次要结局

  • Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Investigator Determined Clinical Response at TOC (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Investigator Determined Clinical Response at LFU (mMITT Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-patient Microbiological Response at LFU (mMITT Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Per-patient Microbiological Response at TOC (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-patient Microbiological Response at LFU (ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Plasma Concentrations for Avibactam Between 300 to 360 Minutes After Dose(PK Analysis Set)(Between 300 to 360 minutes after dose)
  • Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set)(Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.)
  • Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set)(Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.)
  • Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set)(Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.)
  • Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set)(Time to first defervescence is defined as the time (in days) from the first dose of IV study therapy to first absence of fever, which is temperature ≤ 37.8 C in a 24-hour period.)
  • Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set)(At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization)
  • Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set)(At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-pathogen Microbiological Response at LFU for Blood Only (Extended ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set)(At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-pathogen Microbiological Response at TOC for Blood Only (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at LFU for Blood Only (mMITT Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization)
  • Per-pathogen Microbiological Response at EOT (IV) for Blood Only (Extended ME at EOT (IV) Analysis Set)(At EOT IV visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-pathogen Microbiological Response at TOC for Blood Only (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-pathogen Microbiological Response at EOT (IV) for Blood Only (ME at EOT (IV) Analysis Set)(At EOT (IV) visit. EOT (IV) visit is Within 24 hours after completion of the last infusion of IV study therapy and on/before the first dose for oral study therapy)
  • Per-pathogen Microbiological Response at TOC for Blood Only (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization.)
  • Per-pathogen Microbiological Response at LFU for Blood Only (ME at LFU Analysis Set)(At LFU visit. LFU visit is 45 to 52 days from Randomization.)
  • Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (mMITT Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (Extended ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (ME at TOC Analysis Set)(At TOC visit. TOC visit is 21 to 25 days from Randomization)
  • Plasma Concentrations for Ceftazidime Within 15 Minutes Before/After Dose (PK Analysis Set)(within 15 minutes before/after dose)
  • Plasma Concentrations for Ceftazidime Between 30 to 90 Minutes After Dose(PK Analysis Set)(Between 30 to 90 minutes after dose)
  • Plasma Concentrations for Ceftazidime Between 300 to 360 Minutes After Dose(PK Analysis Set)(Between 300 to 360 minutes after dose)
  • Plasma Concentrations for Avibactam Within 15 Minutes Before/After Dose (PK Analysis Set)(within 15 minutes before/after dose)
  • Plasma Concentrations for Avibactam Between 30 to 90 Minutes After Dose(PK Analysis Set)(Between 30 to 90 minutes after dose)

研究者

发起方
Pfizer
申办方类型
Industry
责任方
Sponsor

研究点 (1)

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