Infection, Surgical Site Infection
Conditions
Keywords
Colorectal surgery
Brief summary
The purpose of this study is to evaluate the efficacy and safety of ertapenem sodium compared with ceftriaxone sodium/metronidazole for the prophylaxis of surgical site infection following elective colorectal surgery in Chinese adults. This study is designed to demonstrate that ertapenem sodium is non-inferior to ceftriaxone sodium/metronidazole in this participant population.
Interventions
Ceftriaxone sodium 2 g administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision
DRUGertapenem sodium
Ertapenem sodium 1 g administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision
DRUGplacebo to metronidazole
Placebo (0.9% sodium chloride) administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision
DRUGmetronidazole
Metronidazole 500 mg administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
\- Participant is scheduled to undergo elective colon or colorectal surgery by laparotomy that is scheduled in advance with adequate time prior to surgery to complete preoperative bowel preparation. \- Participant is a Chinese adult between the ages of more than 18 years old and less than 81 years old. \- Participant is highly unlikely to conceive.
Exclusion criteria
* Participant is undergoing emergency colon or colorectal surgery. * Participant requires a second planned colorectal surgery or other surgery requiring antibiotic prophylaxis within the 4-week follow-up period. * Participant is undergoing laparoscopic-assisted surgery. * Participant is undergoing an isolated rectal procedure. * Participant has a decompensated intestinal obstruction. * Participant has active inflammatory bowel disease involving the colon (i.e., ulcerative colitis or Crohn's disease). * Participant is scheduled to undergo an elective colorectal procedure for revision of a previous operation involving a large bowel resection. * Participant has a bacterial infection at the time of surgery. * Participant requires or is anticipated to need the administration of other (nonstudy therapy) systemic antimicrobial therapy within 1 week prior to surgery or at any time during this study. * Participant is anticipated to receive either antibiotic or antiseptic peritoneal lavage during the surgery. * Participant has a history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to ertapenem sodium, ceftriaxone sodium, metronidazole, penicillin, or any cephalosporin, beta(β)-lactam, or nitroimidazole agents. * Participant is breast feeding or plans to breast feed prior to the completion of the study period. * Participant has neutropenia. * Participant with immunosuppression due to an underlying disease, chronic immunosuppressive therapy, or use of high-dose corticosteroids. * Participant has a rapidly progressive or terminal illness. * Participant is considered unlikely to survive through the expected 4-week study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Success of Prophylaxis | From study drug dose (day of surgery) up to 4 weeks post therapy | Percentage of participants who have no signs or symptoms of infection at the surgical site, do not require surgical intervention for infection, and have no need for further antimicrobial therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Favorable Clinical Response | 4 weeks posttreatment | Percentage of participants who have no signs or symptoms of infection at the surgical site and do not require surgical intervention for infection |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ertapenem Ertapenem sodium 1 g administered intravenously (IV) as a single dose followed by matching placebo to metronidazole administered IV as a single dose | 290 |
| Ceftriaxone/Metronidazole Ceftriaxone sodium 2 g administered intravenously (IV) as a single dose followed by metronidazole 500 mg administered IV as a single dose | 297 |
| Total | 587 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Physician Decision | 7 | 4 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Ertapenem | Ceftriaxone/Metronidazole | Total |
|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 11.4 | 59.1 years STANDARD_DEVIATION 12.1 | 59.2 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 125 Participants | 127 Participants | 252 Participants |
| Sex: Female, Male Male | 165 Participants | 170 Participants | 335 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 290 | 18 / 297 |
| serious Total, serious adverse events | 6 / 290 | 14 / 297 |
Outcome results
Primary
Percentage of Participants With Success of Prophylaxis
Percentage of participants who have no signs or symptoms of infection at the surgical site, do not require surgical intervention for infection, and have no need for further antimicrobial therapy
Time frame: From study drug dose (day of surgery) up to 4 weeks post therapy
Population: Primary analysis results are for evaluable-patients-only, defined as patients who received a complete dose of prophylaxis, underwent elective colorectal surgery with completion of bowel preparation procedure, had primary skin closure of the wound, and did not receive any prohibited systemic antibiotics or other prohibited anti-infective agents.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ertapenem | Percentage of Participants With Success of Prophylaxis | 90.4 percentage of participants |
| Ceftriaxone/Metronidazole | Percentage of Participants With Success of Prophylaxis | 90.3 percentage of participants |
95% CI: [-5.2, 5.5]Miettinen and Nurminen
Secondary
Percentage of Participants With Favorable Clinical Response
Percentage of participants who have no signs or symptoms of infection at the surgical site and do not require surgical intervention for infection
Time frame: 4 weeks posttreatment
Population: Population analyzed was participants who had no signs or symptoms of infection at the surgical site and did not require surgical intervention for infection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ertapenem | Percentage of Participants With Favorable Clinical Response | 96.8 percentage of participants |
| Ceftriaxone/Metronidazole | Percentage of Participants With Favorable Clinical Response | 95.5 percentage of participants |
95% CI: [-2.2, 5.1]Miettinen and Nurminen