Intra-abdominal Infections
Conditions
Keywords
Metronidazole, intra-abdominal infection, pelvic inflammatory disease, anaerobe
Brief summary
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.
Interventions
DRUGMetronidazole
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.
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.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 79 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response: Response Rate (Data Review Committee Assessment) | Baseline to EOT (up to 14 days), TOC | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response: Response Rate (Investigator Assessment) | Baseline to EOT (up to 14 days), TOC | 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. |
| Percentage of Participants Who Was Assessed as Appropriate to Continue Treatment (Investigator Assessment) | Baseline to Day 4 | 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. |
| Bacteriological Response: Eradication Rate (Data Review Committee Assessment) | Baseline to Day 4, EOT (up to 14 days), TOC | 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. |
| Bacteriological Response: Eradication Rate (Investigator Assessment) | Baseline to Day 4, EOT (up to 14 days), TOC | 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. |
| Number of Participants Analyzed for Population Pharmacokinetics (PK) of Metronidazole | 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. | Population pharmacokinetic analysis of Metronidazole is conducted by combining current study data with other Metronidazole studies. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metronidazole/Ceftriaxone Metronidazole was administered in combination with ceftriaxone sodium, at a dose of 500 mg three times a day (TID) or four times a day (QID) for refractory or severe infection. Ceftriaxone was administered at the dose of 1 g twice a day (BID) when metronidazole was administered TID, or at dose of 2 g BID when metronidazole was administered QID. The duration of drug administration was 3 to 14 days. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Does not meet entrance criteria | 1 |
| Overall Study | Lack of Efficacy | 1 |
Baseline characteristics
| Characteristic | Metronidazole/Ceftriaxone |
|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 16.9 |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 38 |
| serious Total, serious adverse events | 4 / 38 |
Outcome results
Primary
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.
Time frame: Baseline to EOT (up to 14 days), TOC
Population: Clinical per protocol set consisted of all participants who received at least one dose of study medication, had no significant protocol deviation, and underwent planned assessments. No imputation was used for missing data. n = number of participants assessed that excluding ones evaluated as indeterminate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metronidazole/Ceftriaxone | Clinical Response: Response Rate (Data Review Committee Assessment) | End of Treatment (n=30) | 96.6 percentage of participants |
| Metronidazole/Ceftriaxone | Clinical Response: Response Rate (Data Review Committee Assessment) | Test of Cure (n=30) | 96.7 percentage of participants |
Secondary
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.
Time frame: Baseline to Day 4, EOT (up to 14 days), TOC
Population: Bacteriologic per protocol set consisted of all participants in the clinical per protocol set in whom bacterial pathogens were identified on Day 1 prior to the initial dose. No imputation was used for missing data. n = number of participants assessed that excluding ones evaluated as indeterminate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metronidazole/Ceftriaxone | Bacteriological Response: Eradication Rate (Data Review Committee Assessment) | Day 4 | 100.0 percentage of participants |
| Metronidazole/Ceftriaxone | Bacteriological Response: Eradication Rate (Data Review Committee Assessment) | End of Treatment | 100.0 percentage of participants |
| Metronidazole/Ceftriaxone | Bacteriological Response: Eradication Rate (Data Review Committee Assessment) | Test of Cure | 100.0 percentage of participants |
Secondary
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.
Time frame: Baseline to Day 4, EOT (up to 14 days), TOC
Population: Bacteriologic per protocol set consisted of all participants in the clinical per protocol set in whom bacterial pathogens were identified on Day 1 prior to the initial dose. No imputation was used for missing data. n = number of participants assessed that excluding ones evaluated as indeterminate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metronidazole/Ceftriaxone | Bacteriological Response: Eradication Rate (Investigator Assessment) | Day 4 | 100.0 percentage of participants |
| Metronidazole/Ceftriaxone | Bacteriological Response: Eradication Rate (Investigator Assessment) | EOT | 100.0 percentage of participants |
| Metronidazole/Ceftriaxone | Bacteriological Response: Eradication Rate (Investigator Assessment) | TOC | 100.0 percentage of participants |
Secondary
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.
Time frame: Baseline to EOT (up to 14 days), TOC
Population: Clinical per protocol set consisted of all participants who received at least one dose of study medication, had no significant protocol deviation, and underwent planned assessments. No imputation was used for missing data. n = number of participants assessed that excluding ones evaluated as indeterminate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metronidazole/Ceftriaxone | Clinical Response: Response Rate (Investigator Assessment) | End of Treatment (n=30) | 96.7 percentage of participants |
| Metronidazole/Ceftriaxone | Clinical Response: Response Rate (Investigator Assessment) | Test of Cure (n=29) | 100.0 percentage of participants |
Secondary
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.
Time frame: 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.
Population: No population pharmacokinetic analysis results are available just for the current study.
Secondary
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.
Time frame: Baseline to Day 4
Population: Clinical per protocol set consisted of all participants who received at least one dose of study medication, had no significant protocol deviation, and underwent planned assessments. No imputation was used for missing data. n = number of participants assessed that excluding ones evaluated as indeterminate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metronidazole/Ceftriaxone | Percentage of Participants Who Was Assessed as Appropriate to Continue Treatment (Investigator Assessment) | 100.0 percentage of participants |