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

NCT01370616 | Completed Phase 3 Results

• 1 other identifier: 0826-061
• Study Type: interventional
• Target: 565
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Infection; Diabetic Foot

Keywords

Infection; Diabetes complications; Diabetes wound infection; Soft tissue infection; Osteomyelitis; Diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Favorable Clinical Response Assessments at Discontinuation of Intravenous (IV) Study Therapy (DCIV)

  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.

  Day 5 up to Day 28

Secondary Outcomes (8)

• Percentage of Participants With Favorable Clinical Response Assessments at Day 5 of IV Study Therapy

  Day 5

• 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

• Percentage of Participants With Favorable Microbiological Response Assessments at FUA Day 10 of Post-antibiotic Study Therapy

  Day 15 up to Day 38

• 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

• Percentage of Participants With One or More Adverse Events (AEs)

  Up to day 42

Study Arms (2)

Ertapenem sodium

EXPERIMENTAL

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

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

Piperacillin/tazobactam sodium

ACTIVE COMPARATOR

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

Drug: Piperacillin/tazobactam sodium; Drug: Amoxicillin/clavulunate potassium

Interventions

Ertapenem sodium DRUG

Ertapenem sodium, 1.0 g IV daily over 30 minutes at Hour 0 for 5 to 28 days

Also known as: MK-0826, INVANZ™

Ertapenem sodium

Piperacillin/tazobactam sodium DRUG

Piperacillin/tazobactam sodium, 4.5 g, IV every 8 hours, given over 30 minutes at Hours 0, 8, and 16 for 5 to 28 days

Also known as: Tazocin™

Piperacillin/tazobactam sodium

Piperacillin/tazobactam-matching placebo DRUG

Placebo, IV over 30 minutes, 2 times per day at Hours 8 and 16 for 5 to 28 days

Ertapenem sodium

Amoxicillin/clavulunate potassium DRUG

If clinically indicated, participants may be switched to Amoxicillin/clavulunate potassium 625 mg administered orally, twice daily, from Day 6 to Day 28

Ertapenem sodium; Piperacillin/tazobactam sodium

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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™)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Xu ZR, Ran XW, Xian Y, Yan XD, Yuan GY, Mu SM, Shen JF, Zhang BS, Gan WJ, Wang J. Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non-inferiority trial. J Antimicrob Chemother. 2016 Jun;71(6):1688-96. doi: 10.1093/jac/dkw004. Epub 2016 Feb 16.

  PMID: 26888908 RESULT

MeSH Terms

Conditions

Infections; Diabetic Foot; Diabetes Complications; Soft Tissue Infections; Osteomyelitis; Diabetes Mellitus

Interventions

Ertapenem; L 749345; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Amoxicillin

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine System Diseases; Diabetic Neuropathies; Bone Diseases, Infectious; Bone Diseases; Musculoskeletal Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Penicillanic Acid; Sulfones; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 10, 2011
• Study Start: September 2, 2011
• Primary Completion: December 8, 2013
• Study Completion: December 18, 2013
• Last Updated: August 27, 2018
• Results First Posted: December 2, 2014

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share