Efficacy and Safety of Ertapenem Sodium (MK-0826) Following Colorectal Surgery in Chinese Adults (MK-0826-056)

A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Efficacy and Safety of Ertapenem Sodium (MK-0826) Versus Ceftriaxone Sodium/Metronidazole for the Prophylaxis of Surgical Site Infection Following Elective Colorectal Surgery in Chinese Adults

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.

Study Overview

• Status: Completed
• Conditions: Surgical Site Infection; Infection
• Intervention / Treatment: Drug: ertapenem sodium; Drug: placebo to metronidazole; Drug: ceftriaxone sodium; Drug: metronidazole

• Study Type: Interventional
• Enrollment (Actual): 599
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ertapenem sodium 1 g; Ertapenem sodium 1 g administered intravenously (IV) as a single dose followed by matching placebo to metronidazole administered IV as a single dose	Drug: ertapenem sodium; Ertapenem sodium 1 g administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision; Other Names: MK-0826; INVANZ®; Drug: placebo 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
Active Comparator: Ceftriaxone sodium 2 g; Ceftriaxone sodium 2 g administered intravenously (IV) as a single dose followed by metronidazole 500 mg administered IV as a single dose	Drug: ceftriaxone sodium; Ceftriaxone sodium 2 g administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision; Other Names: Rocephin®; Drug: metronidazole; Metronidazole 500 mg administered IV as a single dose over 30 minutes within 2 hours prior to the initial surgical incision; Other Names: Flagyl®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From study drug dose (day of surgery) up to 4 weeks post therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	4 weeks posttreatment

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Leng XS, Zhao YJ, Qiu HZ, Cao YK, Zhu WH, Shen JF, Paschke A, Dai WM, Caldwell N, Wang J. Ertapenem prophylaxis of surgical site infections in elective colorectal surgery in China: a multicentre, randomized, double-blind, active-controlled study. J Antimicrob Chemother. 2014 Dec;69(12):3379-86. doi: 10.1093/jac/dku302. Epub 2014 Aug 23.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: February 17, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Colorectal surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Wound Infection; Infections; Communicable Diseases; Surgical Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Ceftriaxone; Ertapenem
• Other Study ID Numbers: 0826-056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php