Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006)
Condition: Acute Hematogenous Osteomyelitis
MeSH terms: Osteomyelitis
Intervention: Daptomycin; Vancomycin (or equivalent); Nafcillin (or equivalent)
Intervention description: IV daptomycin Infusion A in 12 to <18 years old (7 mg/kg); in 7 to < 12 year olds (9 mg/kg); in 24 months to <7 year olds (12 mg/kg); in 12 to <24 month olds (12 mg/kg). Infused over 60 minutes ± 10 minutes once daily followed by up to 3 dummy infusions every 6 hours (q6h) infused over 60 (± 10) min to maintain the blind.; IV vancomycin (or equivalent) (Infusions A,B,C,D), 10 to 15 mg/kg, infused over 60 (± 10) minutes q6h (± 1 hour); IV nafcillin (or β-lactam equivalent) (Infusions A,B,C,D) at 100-200 mg/kg/day, in divided doses infused over 60 (± 10) min q6h (± 1 hour)
Intervention MeSH terms: Vancomycin; Daptomycin; Nafcillin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 149.0
Sex: All
Minimum age: 1 Year
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to determine whether daptomycin is effective and safe in the
      treatment of pediatric participants with AHO when compared to vancomycin (or equivalent) or
      nafcillin (or β-lactam equivalent). The primary hypothesis is that daptomycin is non-inferior
      compared with vancomycin (or equivalent) or nafcillin (or β-lactam equivalent) with respect
      to improvement in Pain, Inflammation, and Limb Function on or before study Day 5.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Obtain Informed Consent;

          -  Be 1 year to < 18 years old; a stepwise approach will be implemented to gate
             enrollment as follows: enrollment will begin with children aged 2-17 years; after an
             external Drug Safety Monitoring Board (DSMB) review, enrollment will be broadened to
             1-17 years.

          -  Have diagnosis of suspected or confirmed AHO warranting IV antibacterial therapy as
             inpatient, based on clinical, imaging and/or microbiological evidence as outlined
             below:

        I. Clinical evidence of fever accompanied by symptoms on the affected limb that include but
        it is not limited to pain, tenderness on palpation, inflammation, warmth, swelling,
        difficulty bearing weight, motion restriction, loss of function

        II. Radiologic imaging (magnetic resonance imaging [MRI], bone scan, x-ray, or computed
        tomography [CT] scan) consistent with osteomyelitis OR Microbiological evidence (gram
        stain, culture or polymerase chain reaction (PCR)) from a bone biopsy or bone aspirate (if
        available), or blood

        III. Laboratory evidence: C-reactive protein (CRP) elevated, Erythrocyte sedimentation rate
        (ESR) elevated, leukocytosis or leukopenia, immature neutrophils

        •Confirmed (I, II, and III) OR suspected (I and III) that must be confirmed
        post-randomization

        Participants will not be allowed into the study if they:

          -  Have documented history of any hypersensitivity or allergic reaction to daptomycin

          -  Have septic arthritis only (without AHO)

          -  Have acute hematogenous osteomyelitis that is located in the spine

          -  Have chronic osteomyelitis (i.e. symptoms of osteomyelitis > 21 days) or osteomyelitis
             with complications requiring non-routine surgical treatment (i.e. sequestration).

          -  Have major trauma, penetrating trauma (including a puncture wound of the foot),
             postoperative osteomyelitis, foreign body in or adjacent to affected bone or joint, or
             other iatrogenic bone or joint infections present at the site of infection

          -  Have acute hematogenous osteomyelitis due to a proven gram-negative organism

          -  Have transient tenosynovitis, juvenile rheumatoid arthritis (JRA), reactive arthritis,
             bony tumors, and other osteoarticular diseases suspected to be due to a nonbacterial
             (eg, fungal or mycobacterial) etiology

          -  Receive more than 24 hours of effective intravenous antibacterial therapy for
             osteomyelitis within 96 hours before randomization unless microbiological or clinical
             failure is documented

          -  Require any potentially effective concomitant systemic antibacterial therapy for
             gram-positive infections

          -  Have history of seizures (except febrile seizure of childhood)

          -  Have peripheral neuropathy

          -  Have history of rhabdomyolysis (with the exception of muscle injury due to trauma)

          -  Have Sickle cell anemia

          -  Cannot be assessed clinically during the study

          -  Have any condition (eg, cystic fibrosis, current septic shock) that would make the
             subject, in the opinion of the Investigator, unsuitable for the study

          -  Have significant reduced creatinine clearance (CrCl) < 50 mL/min/1.73 m2

          -  Have evidence of significant hepatic, hematologic, or immunologic dysfunction

          -  Have Creatine kinase (CK) elevation ≥ 10 × ULN (upper limit of normal) without
             symptoms or ≥ 5 × ULN with symptoms

          -  If female, must not be pregnant or nursing and if required by age and life style take
             appropriate measures to not get pregnant during the study.

          -  Have participated in any study involving administration of an investigational agent or
             device or daptomycin within 30 days

          -  Are unable or unwilling to adhere to the study-specified procedures and restrictions

          -  Has suspected or confirmed pneumonia, empyema, meningitis, or endocarditis.