Complicated Intra-abdominal Infections
Conditions
Brief summary
The purpose of this study is to determine whether NXL104 plus ceftazidime is effective in the treatment of complicated intra-abdominal infections as compared to a comparator group.
Interventions
DRUGceftazidime/NXL104 + metronidazole
IV TID
DRUGmeropenem
IV TID
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* complicated intra-abdominal infections
Exclusion criteria
* infections limited to hollow viscus * ischemic bowel disease without perforation * acute suppurative cholangitis * acute necrotizing pancreatitis * pts to undergo stated abdominal repair, open abdomen technique or marsupialization * Apache II \>25
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response at the Test of Cure (TOC) Visit | Test of cure visit: 2 weeks post-therapy (Day 28) | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were microbiologically evaluable (ME) at baseline. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 6 weeks after last dose of study treatment (up to a maximum of 8 weeks) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 weeks after last dose of study treatment that were absent before treatment or that worsened relative to pretreatment state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Microbiological Response at the Test of Cure Visit | Test of cure visit: 2 weeks post-therapy (Day 28) | Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline. |
| Number of Participants With Microbiological Response at the End of IV Therapy | End of IV therapy: From Day 5 to Day 14 | Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline. |
| Number of Participants With Microbiological Response at the Late Follow-up Visit | Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks) | Favorable: eradication (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication (absence of material to culture in a patient who had responded clinically to treatment) |
| Number of Participants With Clinical Response at the End of Intravenous (IV) Therapy | End of IV therapy: From Day 5 to Day 14 | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline. |
| Number of Participants With Clinical Response in CE Participants at the End of IV Therapy | End of IV therapy: From Day 5 to Day 14 | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. |
| Number of Participants With Clinical Response in CE Participants at the Late Follow-up Visit | Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks) | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. |
| Number of Participants With Clinical Response in Clinically Evaluable (CE) Participants at the Test of Cure Visit | Test of cure visit: 2 weeks post-therapy (Day 28) | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. |
| Number of Participants With Clinical Response at the Late Follow-up Visit | Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks) | Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline. |
Countries
Bulgaria, France, India, Lebanon, Poland, Romania, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NXL104/Ceftazidime + Metronidazole Participants received intravenous dose of 500 milligram (mg) of NXL104, 2000 mg of ceftazidime and 500 mg of metronidazole every 8 hour, for up to a maximum duration of 14 days. Participants were followed up to a maximum of 6 weeks post therapy. | 101 |
| Meropenem Participants received intravenous dose of 1000 mg of meropenem every 8 hour, for up to a maximum duration of 14 days. Participants were followed up to a maximum of 6 weeks post therapy. | 102 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Clinical failure | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Protocol deviation | 1 | 0 |
| Overall Study | Randomized but not treated | 1 | 0 |
Baseline characteristics
| Characteristic | NXL104/Ceftazidime + Metronidazole | Meropenem | Total |
|---|---|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 15.93 | 42.6 years STANDARD_DEVIATION 18.09 | 42.8 years STANDARD_DEVIATION 17.01 |
| Sex: Female, Male Female | 31 Participants | 21 Participants | 52 Participants |
| Sex: Female, Male Male | 70 Participants | 81 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 101 | 36 / 102 |
| serious Total, serious adverse events | 9 / 101 | 11 / 102 |
Outcome results
Primary
Number of Participants With Clinical Response at the Test of Cure (TOC) Visit
Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were microbiologically evaluable (ME) at baseline.
Time frame: Test of cure visit: 2 weeks post-therapy (Day 28)
Population: ME set:clinically evaluable(CE)subset with atleast 1 etiologic pathogen isolated from a clinically relevant specimen in initial culture susceptible in both study agents. CE set:participants diagnosed with intraperitoneal infection confirmed by operative findings with adequate therapy and information to determine clinical outcome at specified visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Clinical Response at the Test of Cure (TOC) Visit | 62 participants |
| Meropenem | Number of Participants With Clinical Response at the Test of Cure (TOC) Visit | 71 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 weeks after last dose of study treatment that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to 6 weeks after last dose of study treatment (up to a maximum of 8 weeks)
Population: Safety population included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 65 participants |
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 9 participants |
| Meropenem | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 59 participants |
| Meropenem | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 11 participants |
Secondary
Number of Participants With Clinical Response at the End of Intravenous (IV) Therapy
Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline.
Time frame: End of IV therapy: From Day 5 to Day 14
Population: ME population: A subset of CE population with at least 1 etiologic pathogen isolated from a clinically relevant specimen in initial culture susceptible in both study agents.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Clinical Response at the End of Intravenous (IV) Therapy | 66 participants |
| Meropenem | Number of Participants With Clinical Response at the End of Intravenous (IV) Therapy | 74 participants |
Secondary
Number of Participants With Clinical Response at the Late Follow-up Visit
Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required. This clinical response was measured in participants who were ME at baseline.
Time frame: Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks)
Population: ME population: A subset of CE population with at least 1 etiologic pathogen isolated from a clinically relevant specimen in initial culture susceptible in both study agents.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Clinical Response at the Late Follow-up Visit | 62 participants |
| Meropenem | Number of Participants With Clinical Response at the Late Follow-up Visit | 71 participants |
Secondary
Number of Participants With Clinical Response in CE Participants at the End of IV Therapy
Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required.
Time frame: End of IV therapy: From Day 5 to Day 14
Population: CE population included all randomized participants diagnosed with intraperitoneal infection confirmed by operative findings, received adequate therapy and had information to determine clinical outcome at specified visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Clinical Response in CE Participants at the End of IV Therapy | 84 participants |
| Meropenem | Number of Participants With Clinical Response in CE Participants at the End of IV Therapy | 87 participants |
Secondary
Number of Participants With Clinical Response in CE Participants at the Late Follow-up Visit
Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required.
Time frame: Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks)
Population: CE population included all randomized participants diagnosed with intraperitoneal infection confirmed by operative findings, received adequate therapy and had information to determine clinical outcome at specified visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Clinical Response in CE Participants at the Late Follow-up Visit | 79 participants |
| Meropenem | Number of Participants With Clinical Response in CE Participants at the Late Follow-up Visit | 84 participants |
Secondary
Number of Participants With Clinical Response in Clinically Evaluable (CE) Participants at the Test of Cure Visit
Clinical response was defined as complete resolution or significant improvement of signs and symptoms of the index infection. No further antimicrobial therapy or surgical or radiological intervention was required.
Time frame: Test of cure visit: 2 weeks post-therapy (Day 28)
Population: CE population included all randomized participants diagnosed with intraperitoneal infection confirmed by operative findings, received adequate therapy and had information to determine clinical outcome at specified visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Clinical Response in Clinically Evaluable (CE) Participants at the Test of Cure Visit | 80 participants |
| Meropenem | Number of Participants With Clinical Response in Clinically Evaluable (CE) Participants at the Test of Cure Visit | 85 participants |
Secondary
Number of Participants With Microbiological Response at the End of IV Therapy
Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline.
Time frame: End of IV therapy: From Day 5 to Day 14
Population: ME population: A subset of CE population with at least 1 etiologic pathogen isolated from a clinically relevant specimen in initial culture susceptible in both study agents.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Microbiological Response at the End of IV Therapy | 66 participants |
| Meropenem | Number of Participants With Microbiological Response at the End of IV Therapy | 74 participants |
Secondary
Number of Participants With Microbiological Response at the Late Follow-up Visit
Favorable: eradication (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication (absence of material to culture in a patient who had responded clinically to treatment)
Time frame: Late follow-up visit: 4 to 6 weeks post-therapy (up to 8 weeks)
Population: ME population: A subset of CE population with at least 1 etiologic pathogen isolated from a clinically relevant specimen in initial culture susceptible in both study agents.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Microbiological Response at the Late Follow-up Visit | 62 participants |
| Meropenem | Number of Participants With Microbiological Response at the Late Follow-up Visit | 71 participants |
Secondary
Number of Participants With Microbiological Response at the Test of Cure Visit
Microbiological response was defined as eradication of pathogen identified (absence of causative pathogens from appropriately obtained specimens at site of infection) or presumptive eradication of pathogens (absence of material to culture in a participant who had responded clinically to treatment). This clinical response was measured in participants who were ME at baseline.
Time frame: Test of cure visit: 2 weeks post-therapy (Day 28)
Population: ME population: A subset of CE population with at least 1 etiologic pathogen isolated from a clinically relevant specimen in initial culture susceptible in both study agents.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NXL104/Ceftazidime + Metronidazole | Number of Participants With Microbiological Response at the Test of Cure Visit | 62 participants |
| Meropenem | Number of Participants With Microbiological Response at the Test of Cure Visit | 71 participants |