Urinary Tract Infection
Conditions
Brief summary
The purpose of this study is to determine the efficacy of ertapenem sodium (Invanz) in treatment of complicated urinary tract infections with respect to the proportion of patients with a favorable microbiological response at 5-9 days post therapy.
Interventions
DRUGertapenem sodium (MK0826)
a single daily dose of ertapenem sodium 1.0g IV infused over 30 minutes, for 7-14 days (patients may be switched to oral ciprofloxacin after 3 doses of IV therapy if needed)
DRUGComparator: ceftriaxone sodium
a single daily dose of ceftriaxone 2.0g IV infused over 30 minutes, for 7-14 days (patients may be switched to oral ciprofloxacin after 3 doses of IV therapy)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with a suspected or documented complicated urinary tract infection * Female patients must test negative for pregnancy and agree to use adequate birth control measures * Nursing women must agree to defer breastfeeding until 5 days after completion of all study antibiotic therapy
Exclusion criteria
* Patients with complete obstruction of any portion of the urinary tract * Patients with rapidly progressive or terminal illness * Renal transplant patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiological Response Assessment Profile | 5 to 9 days post-therapy | The difference in favorable microbiological response rates between the 2 treatment groups (MK0826 response rate minus ceftriaxone response rate) was assessed |
| The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Adverse experiences that occurred during the study parenteral therapy period were analyzed. The period of parenteral therapy is from 3 days up to 14 days | Safety was assessed by statistical and/or clinical review of all safety parameters, including adverse experiences, physical examination, vital signs, and laboratory results during parenteral therapy. As per the primary safety hypothesis, it was expected that, at the end of the parenteral therapy only, MK0826 would be similar to ceftriaxone with respect to the proportion of patients with any drug-related clinical or laboratory adverse experiences leading to discontinuation of study drug and also with respect to the proportion of patients with any serious drug-related adverse experiences. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Assessment Profile | 5 to 9 days post-therapy | The difference in favorable clinical response rates between the 2 treatment groups (MK0826 response rate minus ceftriaxone response rate) was assessed |
Participant flow
Recruitment details
Patients were recruited from 9 Medical Centers of Korea between April 2008 and January 2009. Last patient has visited on 27 Feb 2009.
Pre-assignment details
1 patient was excluded due to ineligibility. The patient had a positive at screening pregnancy test.
Participants by arm
| Arm | Count |
|---|---|
| MK0826 A single daily dose of MK0826 1.0 g intravenous infused over 30 minutes, for 7-14 days (patients may be switched to oral ciprofloxacin at a dose of 500 mg twice daily after 3 doses of parentheral therapy) | 135 |
| Ceftriaxone A single daily dose of 2.0 g Ceftriaxone sodium intravenous infused over 30 minutes, for 7-14 days (patients may be switched to oral ciprofloxacin at a dose of 500 mg twice daily after 3 doses of parentheral therapy) | 136 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Another antibiotic therapy required | 0 | 1 |
| Overall Study | Appendectomy | 1 | 0 |
| Overall Study | Clinical adverse experience | 4 | 2 |
| Overall Study | Clinical/microbiologic failure | 1 | 2 |
| Overall Study | Inappropriate therapy duration, < 7 Days | 0 | 1 |
| Overall Study | Inclusion/Exclusion criteria not met | 1 | 3 |
| Overall Study | Laboratory adverse experience | 1 | 1 |
| Overall Study | Negative urine culture | 2 | 0 |
| Overall Study | Pathogen culture = no growth | 26 | 34 |
| Overall Study | Pathogen resistant | 7 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 4 |
Baseline characteristics
| Characteristic | MK0826 | Ceftriaxone | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 19.5 | 56.5 years STANDARD_DEVIATION 17.6 | 55.9 years STANDARD_DEVIATION 18.5 |
| Duration of Symptoms(Days) | 4.1 Days STANDARD_DEVIATION 4.6 | 4.7 Days STANDARD_DEVIATION 6.4 | 4.4 Days STANDARD_DEVIATION 5.6 |
| Sex: Female, Male Female | 119 Participants | 126 Participants | 245 Participants |
| Sex: Female, Male Male | 16 Participants | 10 Participants | 26 Participants |
| Stratum Acute pyelonephritis | 103 participants | 107 participants | 210 participants |
| Stratum Other complicated urinary tract infection | 32 participants | 29 participants | 61 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 85 / 132 | 90 / 135 |
| serious Total, serious adverse events | 12 / 132 | 8 / 135 |
Outcome results
Primary
Microbiological Response Assessment Profile
The difference in favorable microbiological response rates between the 2 treatment groups (MK0826 response rate minus ceftriaxone response rate) was assessed
Time frame: 5 to 9 days post-therapy
Population: Primary efficacy analysis was done for 137 evaluable patients (66 patients from MK0826 and 71 patients from Ceftriaxone)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0826 | Microbiological Response Assessment Profile | 58 Participants |
| Ceftriaxone | Microbiological Response Assessment Profile | 63 Participants |
95% CI: [-11.7, 10.2]
Primary
The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment
Safety was assessed by statistical and/or clinical review of all safety parameters, including adverse experiences, physical examination, vital signs, and laboratory results during parenteral therapy. As per the primary safety hypothesis, it was expected that, at the end of the parenteral therapy only, MK0826 would be similar to ceftriaxone with respect to the proportion of patients with any drug-related clinical or laboratory adverse experiences leading to discontinuation of study drug and also with respect to the proportion of patients with any serious drug-related adverse experiences.
Time frame: Adverse experiences that occurred during the study parenteral therapy period were analyzed. The period of parenteral therapy is from 3 days up to 14 days
Population: Safety Analysis has been done 267 patients who received at least 1 dose of parenteral therapy (132 patients from MK0826 and 135 patients from Ceftriaxone)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK0826 | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Discontinued due to drug-related clinical AEs | 1 Participants |
| MK0826 | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Serious drug-related clinical AEs | 0 Participants |
| MK0826 | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Discontinued due to drug-related laboratory AEs | 1 Participants |
| MK0826 | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Serious drug-related Laboratory AEs | 0 Participants |
| Ceftriaxone | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Serious drug-related Laboratory AEs | 0 Participants |
| Ceftriaxone | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Discontinued due to drug-related clinical AEs | 0 Participants |
| Ceftriaxone | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Discontinued due to drug-related laboratory AEs | 1 Participants |
| Ceftriaxone | The Number of Patients Who Experience Any Drug-related Adverse Experiences Leading to Discontinuation of Parenteral Study Drug and the Number of Patients With Any Drug-related Serious Adverse Experiences (AEs) During Parenteral Treatment | Serious drug-related clinical AEs | 0 Participants |
Secondary
Clinical Response Assessment Profile
The difference in favorable clinical response rates between the 2 treatment groups (MK0826 response rate minus ceftriaxone response rate) was assessed
Time frame: 5 to 9 days post-therapy
Population: Secondary efficacy analysis was done for 137 evaluable patients (66 patients from MK0826 and 71 patients from Ceftriaxone)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0826 | Clinical Response Assessment Profile | 64 Participants |
| Ceftriaxone | Clinical Response Assessment Profile | 70 Participants |
95% CI: [-6.6, 3.2]