search
Back to results

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

Primary Purpose

Infection; Diabetic Foot

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ertapenem sodium
Piperacillin/tazobactam sodium
Piperacillin/tazobactam-matching placebo
Amoxicillin/clavulunate potassium
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infection; Diabetic Foot focused on measuring Infection, Diabetes complications, Diabetes wound infection, Soft tissue infection, Osteomyelitis, Diabetes mellitus

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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™)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Ertapenem sodium

    Piperacillin/tazobactam sodium

    Arm 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

    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

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Percentage of Participants With Favorable Clinical Response Assessments at Day 5 of IV Study Therapy
    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
    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 Microbiological Response Assessments at FUA Day 10 of Post-antibiotic Study Therapy
    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
    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 With One or More Adverse Events (AEs)
    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 Drug-related AEs
    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)
    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 Who Discontinued Treatment Due to an AE
    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.

    Full Information

    First Posted
    June 8, 2011
    Last Updated
    July 27, 2018
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT01370616
    Brief Title
    Ertapenem Sodium (MK-0826) Versus Piperacillin/Tazobactam Sodium for the Treatment of Diabetic Foot Infections in Chinese Adults (MK-0826-061)
    Official Title
    A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial to Study the Efficacy and Safety of Ertapenem Sodium (MK-0826) Versus Piperacillin/Tazobactam Sodium in the Treatment of Diabetic Foot Infections in Chinese Adults
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2, 2011 (Actual)
    Primary Completion Date
    December 8, 2013 (Actual)
    Study Completion Date
    December 18, 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Infection; Diabetic Foot
    Keywords
    Infection, Diabetes complications, Diabetes wound infection, Soft tissue infection, Osteomyelitis, Diabetes mellitus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    565 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ertapenem sodium
    Arm Type
    Experimental
    Arm 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
    Arm Title
    Piperacillin/tazobactam sodium
    Arm Type
    Active Comparator
    Arm 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
    Intervention Type
    Drug
    Intervention Name(s)
    Ertapenem sodium
    Other Intervention Name(s)
    MK-0826, INVANZ™
    Intervention Description
    Ertapenem sodium, 1.0 g IV daily over 30 minutes at Hour 0 for 5 to 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Piperacillin/tazobactam sodium
    Other Intervention Name(s)
    Tazocin™
    Intervention Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Piperacillin/tazobactam-matching placebo
    Intervention Description
    Placebo, IV over 30 minutes, 2 times per day at Hours 8 and 16 for 5 to 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Amoxicillin/clavulunate potassium
    Intervention Description
    If clinically indicated, participants may be switched to Amoxicillin/clavulunate potassium 625 mg administered orally, twice daily, from Day 6 to Day 28
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Favorable Clinical Response Assessments at Discontinuation of Intravenous (IV) Study Therapy (DCIV)
    Description
    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.
    Time Frame
    Day 5 up to Day 28
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Favorable Clinical Response Assessments at Day 5 of IV Study Therapy
    Description
    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.
    Time Frame
    Day 5
    Title
    Percentage of Participants With Favorable Clinical Response Assessments at Follow-up Assessment (FUA) Day 10 of Post-antibiotic Study Therapy
    Description
    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.
    Time Frame
    Day 15 up to Day 38
    Title
    Percentage of Participants With Favorable Microbiological Response Assessments at FUA Day 10 of Post-antibiotic Study Therapy
    Description
    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.
    Time Frame
    Day 15 up to Day 38
    Title
    Percentage of Participants With Both Favorable Clinical and Microbiological Response Assessments at FUA Day 10 of Post-antibiotic Study Therapy
    Description
    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.
    Time Frame
    Day 15 up to Day 38
    Title
    Percentage of Participants With One or More Adverse Events (AEs)
    Description
    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.
    Time Frame
    Up to day 42
    Title
    Percentage of Participants With Drug-related AEs
    Description
    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.
    Time Frame
    Up to day 42
    Title
    Percentage of Participants With Serious AEs (SAEs)
    Description
    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.
    Time Frame
    Up to day 42
    Title
    Percentage of Participants Who Discontinued Treatment Due to an AE
    Description
    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.
    Time Frame
    Up to day 28

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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™)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    26888908
    Citation
    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.
    Results Reference
    result
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=0826-061&kw=0826-061&tab=access

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs