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

Phase 3

Completed

Conditions: Infection; Diabetic Foot

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

Registration Number: NCT01370616

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 565

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™)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Piperacillin/tazobactam sodium	Amoxicillin/clavulunate potassium	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
Piperacillin/tazobactam sodium	Piperacillin/tazobactam sodium	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
Ertapenem sodium	Piperacillin/tazobactam-matching placebo	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
Ertapenem sodium	Amoxicillin/clavulunate potassium	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
Ertapenem sodium	Ertapenem sodium	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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Favorable Clinical Response Assessments at Discontinuation of Intravenous (IV) Study Therapy (DCIV)	Day 5 up to Day 28	The investigator assessed participants for a favorable clinical response, defined as clinical improvement or cure. Clinical improvement means that most pretherapy signs and symptoms of the index infection, in particular fever, lympangitis, and purulent drainage had resolved, and no further IV antibiotic therapy was required. Cure means that all pretherapy signs and symptoms of the index infection had resolved, and no further IV antibiotic therapy was required.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With One or More Adverse Events (AEs)	Up to day 42	An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body that is temporally associated with the use of the investigational product, whether or not considered related to the use of the medicinal product. This also includes any change in frequency and/or intensity of a preexisting condition which is temporally associated with the use of the medicinal product.
Percentage of Participants With Favorable Clinical Response Assessments at Day 5 of IV Study Therapy	Day 5	The investigator assessed participants for a favorable clinical response, defined as clinical improvement or cure. Clinical improvement means that most pretherapy signs and symptoms of the index infection, in particular fever, lympangitis, and purulent drainage had resolved, and no further IV antibiotic therapy was required. Cure means that all pretherapy signs and symptoms of the index infection had resolved, and no further IV antibiotic therapy was required.
Percentage of Participants With Favorable Clinical Response Assessments at Follow-up Assessment (FUA) Day 10 of Post-antibiotic Study Therapy	Day 15 up to Day 38	The investigator assessed participants for a favorable clinical response, defined as clinical improvement or cure. Clinical improvement means that most pretherapy signs and symptoms of the index infection, in particular fever, lympangitis, and purulent drainage had resolved, and no further IV antibiotic therapy was required. Cure means that all pretherapy signs and symptoms of the index infection had resolved, and no further IV antibiotic therapy was required.
Percentage of Participants With Drug-related AEs	Up to day 42	A drug-related AE is any AE caused by the test drug as determined by an investigator who is a qualified physician. Drug-relatedness of the AE was assessed by evidence that the participant was actually exposed to the test drug, whether the AE followed a reasonable temporal sequence from administration of the test drug, and whether or not the AE was more reasonably explained by another source.
Percentage of Participants With Serious AEs (SAEs)	Up to day 42	A SAE is an AE occurring at any dose that resulted in any of the following: death, was life threatening, a persistent or significant disability/incapacity, prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect in an offspring, was a cancer, an overdose, or other important medical events requiring medical or surgical intervention.
Percentage of Participants With Favorable Microbiological Response Assessments at FUA Day 10 of Post-antibiotic Study Therapy	Day 15 up to Day 38	The investigator assessed participants for a favorable microbiological response, defined as eradication or presumptive eradication. Eradication means that the original pathogen was absent from the last available culture of an adequate specimen obtained from the original site of infection. Presumptive eradication means that the participant showed cure or improvement and no appropriate material is available to follow-up culture from the original site of infection, or collection of such a specimen would cause undue discomfort.
Percentage of Participants With Both Favorable Clinical and Microbiological Response Assessments at FUA Day 10 of Post-antibiotic Study Therapy	Day 15 up to Day 38	The investigator assessed participants for both a favorable clinical response (clinical improvement or cure) and a favorable microbiological response (eradication or presumptive eradication). Clinical improvement means that most pretherapy signs and symptoms of the index infection, had resolved, and no further IV antibiotic therapy is required. Cure means that all pretherapy signs and symptoms of the index infection had resolved, and no further IV antibiotic therapy was required. Eradication means that the original pathogen was absent from the last available culture obtained from the original site of infection. Presumptive eradication means that the participant showed cure or improvement and no appropriate material is available to follow-up culture from the original site of infection, or collection of such a specimen would cause undue discomfort.
Percentage of Participants Who Discontinued Treatment Due to an AE	Up to day 28	Participants chose to discontinue treatment or were discontinued from the study by the investigator due to any untoward effects, or for safety reasons such as an AE. The investigator determined whether or not the AE caused the test drug to be discontinued.