Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006)
Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006)
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.
Acute hematogenous osteomyelitis is a common problem in the pediatric population, affecting
 approximately 5/10,000 children each year and accounting for approximately 1% of all
 pediatric hospitalizations. In children, osteomyelitis arises from bacteremic seeding of the
 bone metaphysis.

 Daptomycin, is a cyclic lipopeptide antibacterial active against most clinically significant
 gram-positive pathogens including drug-resistant strains such as Methicillin Resistant
 Staphylococcus (S.) aureus (MRSA) and Methicillin Susceptible S. aureus (MSSA). Daptomycin
 has proven clinical efficacy in adults in the treatment of complicated skin and skin
 structure infections (cSSSI) caused by aerobic gram-positive pathogens and the treatment of
 S. aureus bloodstream infections (bacteremia; SAB), including those complicated by
 right-sided infective endocarditis, caused by MSSA and MRSA. Although not indicated for
 osteomyelitis, daptomycin has been successfully used to treat osteoarticular infections in
 adults and children as salvage therapy and at medical centers with increasingly high rates of
 vancomycin resistant organisms.

 In addition, more comparative clinical trials are needed in pediatric AHO to better elucidate
 the optimal treatment regimen and clinical response.
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.