Ertapenem Sodium (MK-0826) Versus Piperacillin/Tazobactam Sodium for the Treatment of Diabetic Foot Infections in Chinese Adults (MK-0826-061)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Infection; Diabetic Foot

Treatments: Drug: Ertapenem sodium; Drug: Piperacillin/tazobactam sodium; Drug: Piperacillin/tazobactam-matching placebo; Drug: Amoxicillin/clavulunate potassium

Study type: Interventional

Funder types: Industry

Identifiers

NCT01370616

0826-061

Details and patient eligibility

About

This study compared ertapenem sodium to piperacillin/tazobactam sodium for the treatment of moderate to severe diabetic foot infections. The primary hypothesis was that treatment with ertapenem sodium is non-inferior to treatment with piperacillin/tazobactam sodium, in achieving clinical improvement or cure.

Enrollment: 565 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participant is Chinese with:

• Type I diabetes mellitus (IDDM) or Type II diabetes mellitus (NIDDM) treated with diet and/or medication
• Clinically- or bacteriologically-documented moderate-to-severe (non life-threatening) diabetic foot infection that requires treatment with IV antibiotics
• Wound site or lesion with purulent drainage from the primary site of infection OR at least 3 of the following: fever, white blood count (WBC) >10,000 with >5% immature neutrophils, local periwound erythema (redness) extending >1 cm away from the wound edge or abscess cavity, localized periwound edema (swelling), localized tenderness or pain, localized fluctuance, lymphangitis associated with a skin lesion, localized warmth, and localized induration (limb brawny edema)
• Negative skin test result for allergy to penicillin

Exclusion criteria

• Pregnant, breastfeeding, or intending to become pregnant or father a child during the course of the study
• Presence of uncomplicated skin infection such as the following: simple abscesses, impetigo, furunculosis, carbunculosis, or folliculitis in normal hosts; infected burn wound; necrotizing fasciitis; suspected osteomyelitis contiguous with the skin or skin structure infection for which removal of the infected bone is not likely to occur within 2 days of initiation of IV study therapy; wound infection that contains concomitant gangrene that cannot be adequately removed with debridement; infection likely to require a below-the-knee amputation (BKA); infection involving prosthetic material; or evidence of indwelling foreign material (such as prosthetic or surgical hardware) near the infected site that cannot be removed by surgical debridement
• Treatment within 3 days prior to the eligibility screening with >24 hours of systemic antibiotic therapy known to be effective against the presumed or documented etiologic pathogen(s)
• History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to carbapenem antibiotics (such as ertapenem sodium, imipenem cilastatin, meropenem, or doripenem) piperacillin/tazobactam sodium, amoxicillin/clavulanate, any penicillins, any cephalosporins, or any other β-lactam agents
• Need for concomitant systemic antibacterial(s) in addition to those designated in the 2 study groups (with the exception of the addition of vancomycin for Enterococcus ssp. or methicillin-resistant Staphylococcus aureus [MRSA])
• Insufficient vascular perfusion to the affected limb
• Rapidly progressive or terminal illness
• Requirement or anticipation of need for dialysis (peritoneal dialysis, hemodialysis, or hemofiltration)
• Acute hepatitis or acute decompensation of chronic hepatitis
• Human immunodeficiency virus (HIV)-positive with a clinical diagnosis of acquired immune deficiency syndrome (AIDS), or an absolute neutrophil count (ANC) of <1000 cells/mm^3
• Immunosuppression
• Participation in any other clinical study involving the administration of an investigational medication within 30 days
• Participation in any other clinical study involving ertapenem sodium (INVANZ™)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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565 participants in 2 patient groups

Ertapenem sodium

Experimental group

Description:

Participants received 1.0 g intravenous (IV) ertapenem sodium as a single daily dose at Hour 0 infused over a 30-minute interval , and IV piperacillin/tazobactam-matching placebo at Hours 8 and 16 infused over a 30-minute interval, for 5 to 28 days. Participants may be switched to Amoxicillin/clavulunate potassium 625 mg administered orally, twice daily, from Day 6 to Day 28

Treatment:

Drug: Piperacillin/tazobactam-matching placebo

Drug: Amoxicillin/clavulunate potassium

Drug: Ertapenem sodium

Piperacillin/tazobactam sodium

Active Comparator group

Description:

Participants received 4.5 g IV piperacillin/tazobactam at Hours 0, 8, and 16 infused over a 30-minute interval, for 5 to 28 days. Participants may be switched to Amoxicillin/clavulunate potassium 625 mg administered orally, twice daily, from Day 6 to Day 28

Treatment:

Drug: Piperacillin/tazobactam sodium

Drug: Amoxicillin/clavulunate potassium