Clinical Trial: Compare Ceftazidime-Avibactam + Metronidazole Versus Meropenem for Hospitalized Adults With Complicated Intra-Abdominal Infections

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Vers

Brief Summary: The purpose of this study is to evaluate the effects of Ceftazidime Avibactam plus Metronidazole compared to Meropenem for treating hospitalized patients with complicated intra-abdominal infections.

Detailed Summary: A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults
Sponsor: AstraZeneca

Current Primary Outcome:

  • Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). [ Time Frame: TOC: 28 to 35 days after start of study drug ]
    The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention is necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, death where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA.
  • Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). [ Time Frame: TOC: 28 to 35 days after start of study drug ]
    The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure.
  • Clinical Response

    Original Primary Outcome: Clinical Cure as Measured by proportion of patients meeting cure criteria in the microbiological modified Intent-To-Treat analysis set. [ Time Frame: 28 to 35 days after start of study drug ]

    Current Secondary Outcome:

    • Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set [ Time Frame: TOC: 28 to 35 days after start of study drug ]
      The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
    • Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set [ Time Frame: TOC: 28 to 35 days after start of study drug ]
      The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
    • Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) [ Time Frame: EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU: 42 to 49 days after start of study drug ]
      Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure.
    • Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set [ Time Frame: EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU 42 to 49 days after start of study drug ]
      Microbiological responses as per the protocoled criteria: responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to a surgical review panel (SRP) assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    • Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. [ Time Frame: TOC: 28 to 35 days after start of study drug. ]
      The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
    • Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set [ Time Frame: Test of Cure: 28 to 35 days after start of study drug ]
      Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
    • Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set [ Time Frame: TOC: 28 to 35 days after start of study drug ]
      The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
    • Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set [ Time Frame: Test of Cure: 28 to 35 days after start of study drug ]
      Microbiological responses other than "indeterminate" were classified as "favorable" or "unfavorable." Favorable microbiological response assessments included "eradication" and "presumed eradication." Unfavorable microbiological response assessments included "persistence," "persistence with increasing minimum inhibitory concentration (MIC)," and "presumed persistence." Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
    • Number o

      Original Secondary Outcome:

      • The proportion of patients with clinical cure in the microbiologically evaluable analysis set. [ Time Frame: 28 to 35 days after start of study drug ]
      • The proportion of patients with clinical cure in the microbiological modified intent-to-treat and microbiologically evaluable analysis sets. [ Time Frame: within 24 hours after last dose of study drug and 42 to 49 days after start of study drug ]
      • The proportion of patients with clinical cure in the clinically evaluable analysis set. [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug ]
      • The proportion of patients with a favorable per-patient microbiological response in the microbiological modified intent to treat and microbiologically evaluable analysis sets [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug ]
      • The proportion of favorable per-pathogen microbiological response in the microbiological modified intent to treat and microbiologically evaluable analysis sets. [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug ]
      • The favorable per-pathogen microbiologic response by minimum inhibitory concentration (MIC) categories in the microbiological modified intent to treat and microbiologically evaluable analysis sets [ Time Frame: within 24 hours after last dose of study drug, 28 to 35 days after start of study drug and 42 to 49 days after start of study drug ]
      • The favorable per-patient clinical response and favorable per-patient microbiological response for patients infected with ceftazidime-resistant pathogens in the microbiological modified intent to treat and microbiologically evaluable analysis sets. [ Time Frame: 28 to 35 days after start of study drug ]
      • The proportion of patients with a favorable per-pathogen microbiological response for patients infected with ceftazidime-resistant pathogens in the microbiological modified intent to treat and microbiologically evaluable analysis sets [ Time Frame: 28 to 35 days after start of study drug ]
      • The time to first defervescence in the clinically evaluable and microbiologically evaluable analysis sets for patients who have fever at study entry. [ Time Frame: 1 to 14 days after start of study drug ]
      • The safety and tolerability by incidence and severity of adverse events and serious adverse events, vital signs, clinical laboratory tests, ECGs and physical exams. [ Time Frame: study duration (from screening visit (Day -1) through last follow up visit (up to 50 days) ]


      Information By: AstraZeneca

      Dates:
      Date Received: December 19, 2011
      Date Started: March 2012
      Date Completion:
      Last Updated: July 1, 2016
      Last Verified: July 2016