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Dalbavancin vs Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis (AHOM)

Primary Purpose

Osteomyelitis

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Dalbavancin
cefazolin, nafcillin, oxacillin or vancomycin
Sponsored by
Durata Therapeutics International BV (an Affiliate of Actavis, Inc.)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteomyelitis

Eligibility Criteria

2 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female 2-16 yrs
  2. diagnosis of Acute Hematogenous Osteomyelitis (AHOM) of the long bones (ulna, radius, femur, tibia) defined by the following clinical signs and symptoms (< 2 weeks in duration; multiple sites of infection within long bones):
  3. Limb abnormality: Pain, point tenderness upon palpation, motion restriction, loss of function
  4. Magnetic resonance imaging (MRI) -OR- Gram-positive cocci documented on a Gram-stain from a bone specimen or from blood cultures.
  5. Elevated C-Reactive Protein (CRP)
  6. informed consent
  7. willing and able to comply with the study protocol
  8. Life Expectancy with appropriate antibiotic therapy and thru study duration

Exclusion Criteria:

  1. Treatment with an investigational drug within 30 days preceding the first dose of study medication.
  2. Receipt of > 24 hours of potentially effective intravenous antibacterial therapy for AHOM within 96 hours before randomization, unless the pathogen isolated was documented to be Methicillin resistant Staphylococcus aureus (MRSA) that was resistant to the administered antibiotic.
  3. Evidence of subacute or chronic osteomyelitis including: symptoms > 2 weeks in duration
  4. AHOM of non-long bones (e.g., pelvis or spine).
  5. Extraosseous findings such as: subperiosteal abscess, pyomyositis, venous thrombosis, or pulmonary embolism.
  6. Previous history of septic arthritis or osteomyelitis.
  7. Major trauma, open-fracture, puncture wound of the foot, post-operative osteomyelitis, foreign body in or adjacent to affected bone or joint, or other iatrogenic bone or joint infections present at the site of infection.
  8. Septic arthritis that is non-contiguous to osteomyelitis
  9. Immunosuppression/immune deficiency
  10. Evidence of Gram-negative bacteria by gram stain in the absence of Gram-positive organisms; fungus or mycobacteria at baseline.
  11. Gram-negative bacteremia, even in the presence of gram-positive infection or gram-positive bacteremia.
  12. A history of oral ulcers preceding the onset of musculoskeletal findings, recent gastrointestinal surgery (within 2 months)
  13. Infection due to an organism known prior to study entry to be not susceptible to dalbavancin (dalbavancin mean inhibitory concentration > 0.12 µg/mL) or vancomycin (vancomycin mean inhibitory concentration (MIC) > 2 μg/mL).
  14. Concomitant systemic antibacterial therapy for Gram-positive infections (eg. Rifampin, gentamicin).
  15. Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.
  16. Sickle cell anemia.
  17. Cystic fibrosis.
  18. hypersensitivity to glycopeptide antibiotics.
  19. not expected to survive for 3 months.
  20. Positive urine (or serum) pregnancy test
  21. Women of Child Bearing Potential who are unwilling or unable to use adequate contraceptive precautions.
  22. Other severe acute or chronic medical or psychiatric condition would make the patient inappropriate for entry into this study.
  23. Unwilling or unable to follow study procedures.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Dalbavancin

    4 Comparators

    Arm Description

    Patients with Creatine Clearance (CrCl) greater than 30 mL/min and patients receiving regular hemodialysis or peritoneal dialysis will receive 15 mg/kg Intravenous (IV) dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1500 mg per administration in children at least 12 years and not to exceed 1000 mg per administration in children less than 12 years of age. • Patients with CrCl < 30 mL/min who are not receiving regular hemodialysis or peritoneal dialysis will receive 10 mg/kg IV dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1000 mg per administration in children at least 12 years and not to exceed 750 mg per administration in children less than 12 years of age. Additionally, subjects randomized to the dalbavancin group will receive an IV placebo infusion at times corresponding to comparator group dosage times for the first eight days.

    cefazolin, oxacillin, nafcillin or vancomycin according to the commercial label Patients with normal renal function will receive either vancomycin 15 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour) not to exceed a daily total dose of 4000 mg, with dose adjustment based on local standard of care to achieve serum trough concentrations of 10 μg/mL to 20 μg/mL; or cefazolin 25 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour); or nafcillin or oxacillin 50 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour).

    Outcomes

    Primary Outcome Measures

    Number of patients with clinical improvement at Day 8

    Secondary Outcome Measures

    Number of clinical responders
    Average reduction in C-reactive Protein (CRP) relative to the highest value
    Number of clinical responders by pathogen
    Number of Participants with Adverse Events

    Full Information

    First Posted
    January 10, 2015
    Last Updated
    September 22, 2016
    Sponsor
    Durata Therapeutics International BV (an Affiliate of Actavis, Inc.)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02344511
    Brief Title
    Dalbavancin vs Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis
    Acronym
    AHOM
    Official Title
    A Phase 3, Multicenter, Double-Blind, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin Versus Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis of the Long Bones Known or Suspected to be Due to Gram-Positive Organisms
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2016
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    March 2016 (undefined)
    Primary Completion Date
    October 2018 (Anticipated)
    Study Completion Date
    April 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Durata Therapeutics International BV (an Affiliate of Actavis, Inc.)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Dalbavancin for Pediatric Osteomyelitis
    Detailed Description
    A Phase 3, Multicenter, Double-Blind, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with Acute Hematogenous Osteomyelitis of the Long Bones Known or Suspected to be due to Gram-Positive Organisms.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Osteomyelitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Dalbavancin
    Arm Type
    Experimental
    Arm Description
    Patients with Creatine Clearance (CrCl) greater than 30 mL/min and patients receiving regular hemodialysis or peritoneal dialysis will receive 15 mg/kg Intravenous (IV) dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1500 mg per administration in children at least 12 years and not to exceed 1000 mg per administration in children less than 12 years of age. • Patients with CrCl < 30 mL/min who are not receiving regular hemodialysis or peritoneal dialysis will receive 10 mg/kg IV dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1000 mg per administration in children at least 12 years and not to exceed 750 mg per administration in children less than 12 years of age. Additionally, subjects randomized to the dalbavancin group will receive an IV placebo infusion at times corresponding to comparator group dosage times for the first eight days.
    Arm Title
    4 Comparators
    Arm Type
    Active Comparator
    Arm Description
    cefazolin, oxacillin, nafcillin or vancomycin according to the commercial label Patients with normal renal function will receive either vancomycin 15 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour) not to exceed a daily total dose of 4000 mg, with dose adjustment based on local standard of care to achieve serum trough concentrations of 10 μg/mL to 20 μg/mL; or cefazolin 25 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour); or nafcillin or oxacillin 50 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour).
    Intervention Type
    Drug
    Intervention Name(s)
    Dalbavancin
    Other Intervention Name(s)
    Dalvance
    Intervention Description
    Drug
    Intervention Type
    Drug
    Intervention Name(s)
    cefazolin, nafcillin, oxacillin or vancomycin
    Intervention Description
    Standard of Care
    Primary Outcome Measure Information:
    Title
    Number of patients with clinical improvement at Day 8
    Time Frame
    Day 8
    Secondary Outcome Measure Information:
    Title
    Number of clinical responders
    Time Frame
    Day 8
    Title
    Average reduction in C-reactive Protein (CRP) relative to the highest value
    Time Frame
    Day 8
    Title
    Number of clinical responders by pathogen
    Time Frame
    Day 8
    Title
    Number of Participants with Adverse Events
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    2 Years
    Maximum Age & Unit of Time
    16 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female 2-16 yrs diagnosis of Acute Hematogenous Osteomyelitis (AHOM) of the long bones (ulna, radius, femur, tibia) defined by the following clinical signs and symptoms (< 2 weeks in duration; multiple sites of infection within long bones): Limb abnormality: Pain, point tenderness upon palpation, motion restriction, loss of function Magnetic resonance imaging (MRI) -OR- Gram-positive cocci documented on a Gram-stain from a bone specimen or from blood cultures. Elevated C-Reactive Protein (CRP) informed consent willing and able to comply with the study protocol Life Expectancy with appropriate antibiotic therapy and thru study duration Exclusion Criteria: Treatment with an investigational drug within 30 days preceding the first dose of study medication. Receipt of > 24 hours of potentially effective intravenous antibacterial therapy for AHOM within 96 hours before randomization, unless the pathogen isolated was documented to be Methicillin resistant Staphylococcus aureus (MRSA) that was resistant to the administered antibiotic. Evidence of subacute or chronic osteomyelitis including: symptoms > 2 weeks in duration AHOM of non-long bones (e.g., pelvis or spine). Extraosseous findings such as: subperiosteal abscess, pyomyositis, venous thrombosis, or pulmonary embolism. Previous history of septic arthritis or osteomyelitis. Major trauma, open-fracture, puncture wound of the foot, post-operative osteomyelitis, foreign body in or adjacent to affected bone or joint, or other iatrogenic bone or joint infections present at the site of infection. Septic arthritis that is non-contiguous to osteomyelitis Immunosuppression/immune deficiency Evidence of Gram-negative bacteria by gram stain in the absence of Gram-positive organisms; fungus or mycobacteria at baseline. Gram-negative bacteremia, even in the presence of gram-positive infection or gram-positive bacteremia. A history of oral ulcers preceding the onset of musculoskeletal findings, recent gastrointestinal surgery (within 2 months) Infection due to an organism known prior to study entry to be not susceptible to dalbavancin (dalbavancin mean inhibitory concentration > 0.12 µg/mL) or vancomycin (vancomycin mean inhibitory concentration (MIC) > 2 μg/mL). Concomitant systemic antibacterial therapy for Gram-positive infections (eg. Rifampin, gentamicin). Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study. Sickle cell anemia. Cystic fibrosis. hypersensitivity to glycopeptide antibiotics. not expected to survive for 3 months. Positive urine (or serum) pregnancy test Women of Child Bearing Potential who are unwilling or unable to use adequate contraceptive precautions. Other severe acute or chronic medical or psychiatric condition would make the patient inappropriate for entry into this study. Unwilling or unable to follow study procedures.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Alena Jamdourek, MD
    Organizational Affiliation
    Durata Therapeutics Inc., an affiliate of Allergan plc
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    Dalbavancin vs Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis

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