A Phase 3 Study Of Intravenous Metronidazole For Intrabdominal Infection

A Phase 3, Multicenter, Unblind, Non-Comparative Study To Confirm Efficacy And Safety Of Intravenous Metronidazole In Patients With Intrabdominal Infection In Combination With Intravenous Ceftriaxone

The purpose of this study is to evaluate the clinical efficacy and safety in Japanese adult subjects with Intra-abdominal/Pelvic infections receiving Metronidazole IV 1,500-2,000 mg/day in combination with ceftriaxone sodium.

Study Overview

• Status: Completed
• Conditions: Intra-abdominal Infections
• Intervention / Treatment: Drug: Metronidazole; Drug: Ceftriaxone sodium

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan
    • National Hospital Organization Kumamoto Medical Center
  • Aichi
    • Ichinomiya, Aichi, Japan
      • Daiyukai First Hospital
  • Aomori
    • Hirosaki, Aomori, Japan
      • Hirosaki National Hospital
  • Chiba-ken
    • Chiba-shi, Chiba-ken, Japan
      • National Hospital Organization Chiba Medical Center
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan
      • National Hospital Organization Kokura Medical Center
  • Hiroshima
    • Fukuyama, Hiroshima, Japan
      • National Hospital Organization Fukuyama Medical Center
  • Ibaraki
    • Hitachi, Ibaraki, Japan
      • Hitachi General Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan
      • Kawasaki Saiwai Hospital
  • Kumamoto
    • Koushi, Kumamoto, Japan
      • Kumamoto Saishunso National Hospital
  • Miyagi-ken
    • Sendai-shi, Miyagi-ken, Japan
      • National Hospital Organization Sendai Medical Center
  • Nagano
    • Iida, Nagano, Japan
      • Iida Municipal Hospital
  • Nagano-ken
    • Suzaka-shi, Nagano-ken, Japan
      • Nagano Prefectural Suzaka Hospital
  • Nagasaki
    • Ohmura, Nagasaki, Japan
      • National Hospital Organization Nagasaki Medical Center
  • Osaka
    • Kawachinagano, Osaka, Japan
      • National Hospital Organization Osaka Minami Medical Center
  • Saitama
    • Koshigaya, Saitama, Japan
      • Koshigaya Municipal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 79 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 16 years of age or older.
• Diagnosed with intra-abdominal infections or pelvic inflammatory diseases.
• Can be obtained a specimen for bacteriological efficacy assessment.

Exclusion Criteria:

• Known or suspected hypersensitivity, intolerance or contraindication to Metronidazole, Ceftriaxone sodium, or other cephem antibiotics.
• Severe renal dysfunction (creatinine clearance < 30 mL/min.) Reference: Cockcroft-Gault calculation formula.
• Hepatic dysfunction (AST, ALT, total bilirubin > 3 times upper limit of normal range values).
• Severe underlying disease; patients in which drug clinical evaluation is difficult because of confounding diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Metronidazole; Metronidazole will be administered at a dose of 500 mg TID (or QID for refractory or severe infection) in combination with ceftriaxone sodium

Drug: Metronidazole; Metronidazole will be administered at a dose of 500 mg TID (or QID for refractory or severe infection) for 3 to 14 days, in principle. Treatment duration can be prolonged up to 21 days based on subject's condition.; Drug: Ceftriaxone sodium; Ceftriaxone sodium will be administered at a daily dose of 2 g (strength) when metronidazole is administered TID or at a daily dose of 4 g (strength) when metronidazole is administered QID.; Other Names: ROCEPHIN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response: Response Rate (Data Review Committee Assessment)	Clinical response was evaluated by the data review committee as effective (cured or improved), ineffective (not meeting "effective" criteria), or indeterminate at the end of treatment (EOT) and the test of cure (TOC: 7 days after EOT) based on clinical symptoms, ultrasound images and necessity of other treatment. TOC was the primary analysis of this outcome measure. Cured = clinical symptoms and abnormal findings at the start of the study were disappeared and considered other antibiotics were not required during the study and after the assessment time point. Improved = clinical symptoms and abnormal findings at the start of the study were improved and considered other antibiotics were not required during the study and after the assessment time point. Response rate was calculated from the following formula; "number of participants evaluated as effective" over "total number of participants that excluding ones evaluated as indeterminate" multiplied by 100.	Baseline to EOT (up to 14 days), TOC

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response: Response Rate (Investigator Assessment)	Clinical response was evaluated by the investigator as effective (cured or improved), ineffective (not meeting "effective" criteria), or indeterminate at the end of treatment (EOT) and the test of cure (TOC: 7 days after EOT) based on clinical symptoms, ultrasound images and necessity of other treatment. TOC was the primary analysis of this outcome measure. Cured = clinical symptoms and abnormal findings at the start of the study were disappeared and considered other antibiotics were not required during the study and after the assessment time point. Improved = clinical symptoms and abnormal findings at the start of the study were improved and considered other antibiotics were not required during the study and after the assessment time point. Response rate was calculated from the following formula; "number of participants evaluated as effective" over "total number of participants that excluding ones evaluated as indeterminate" multiplied by 100.	Baseline to EOT (up to 14 days), TOC
Percentage of Participants Who Was Assessed as Appropriate to Continue Treatment (Investigator Assessment)	The appropriateness of treatment continuation was evaluated on Day 4 by the investigator as continuation, discontinuation or indeterminate based on the clinical response. The percentage of participants was calculated from the following formula; "number of participants assessed as continuation" over "total number of participants that excluding ones assessed as indeterminate" multiplied by 100.	Baseline to Day 4
Bacteriological Response: Eradication Rate (Data Review Committee Assessment)	Bacteriological response was evaluated as eradication (eradication, presumed eradication or colonization), persistence, or indeterminate by the data review committee, at Day 4, at the end of treatment (EOT), and the test of cure (TOC: 7 days after EOT). Eradication Rate was calculated from the following formula, "number of participants with bacteria eradication, presumed eradication or colonization" over "total number of participants that excluding ones evaluated as indeterminate" multiplied by 100.	Baseline to Day 4, EOT (up to 14 days), TOC
Bacteriological Response: Eradication Rate (Investigator Assessment)	Bacteriological response was evaluated as eradication (eradication, presumed eradication or colonization), persistence, or indeterminate by the investigator at the end of treatment (EOT), and the test of cure (TOC: 7 days after EOT). Eradication Rate was calculated from the following formula, "number of participants with bacteria eradication, presumed eradication or colonization" over "total number of participants that excluding ones evaluated as indeterminate" multiplied by 100.	Baseline to Day 4, EOT (up to 14 days), TOC
Number of Participants Analyzed for Population Pharmacokinetics (PK) of Metronidazole	Population pharmacokinetic analysis of Metronidazole is conducted by combining current study data with other Metronidazole studies.	Four samples were taken at any infusion after the first dosing: during infusion, immediately after end of infusion, between 15 and 60 minutes after end of infusion, and between 2 hours and immediately before the start of the next infusion.

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Mikamo H, Matsumizu M, Nakazuru Y, Nagashima M. Efficacy and safety of metronidazole injection for the treatment of infectious peritonitis, abdominal abscess and pelvic inflammatory diseases in Japan. J Infect Chemother. 2015 Feb;21(2):96-104. doi: 10.1016/j.jiac.2014.10.005. Epub 2014 Nov 28.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: October 11, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Estimate): January 24, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Metronidazole; pelvic inflammatory disease; intra-abdominal infection; anaerobe
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Intraabdominal Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Ceftriaxone
• Other Study ID Numbers: A6831005