Safety and Efficacy Study of Daptomycin When Compared to Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Cubist Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01922011
First received: August 9, 2013
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

The purpose of the study is to determine whether daptomycin is effective and safe in the treatment of pediatric subjects with Acute Hematogenous Osteomyelitis (AHO) when compared to vancomycin or nafcillin (or β-lactam equivalent).


Condition Intervention Phase
Acute Hematogenous Osteomyelitis
Drug: Daptomycin
Drug: Vancomycin
Drug: nafcillin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blinded Comparative Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Daptomycin Versus Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis Due to Gram-Positive Organisms

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • Efficacy of daptomycin measured by clinical improvement in the 3 general categories of Pain, Inflammation, and Limb Function based on the Investigator's overall assessment of severity of each of the symptom categories. [ Time Frame: Study day 5 ] [ Designated as safety issue: No ]
    The Investigator will assess the general categories and clinical symptom parameters of AHO once at baseline; twice daily while subject is hospitalized and receiving IV study drug.


Secondary Outcome Measures:
  • Efficacy of daptomycin versus comparator in pediatric subjects with AHO [ Time Frame: Baseline (within 48 hours prior to first dose of IV study drug) - Test of Cure (21-35 days after last dose of IV study drug) ] [ Designated as safety issue: No ]
    1. Clinical improvement as composite end point of pain, inflammation, limb function, body temperature, and C-reactive protein measured at End of IV, End of Therapy, and Test of Cure.
    2. Microbiological outcome at Test of Cure
    3. Microbiological outcome by baseline pathogen at Test of Cure
    4. Sustained clinical improvement at End of Therapy and Test of Cure


Other Outcome Measures:
  • Safety of daptomycin [ Time Frame: The first dose of IV study drug - the final follow-up visit at 6 months ] [ Designated as safety issue: Yes ]
    Measured as incidence of Adverse events (AEs), serious adverse events (SAEs), deaths, and discontinuations due to AEs; changes in vital signs and focused neurological examinations; laboratory evaluations.

  • The pharmacokinetics of daptomycin in pediatric subjects with AHO [ Time Frame: Study Day 3 ] [ Designated as safety issue: No ]
    Blood samples will be collected to measure the plasma concentrations of daptomycin.


Estimated Enrollment: 204
Study Start Date: September 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention Drug: Daptomycin
IV daptomycin dosed at 7,9, or 12 mg/kg infused over 60 minutes ± 10 minutes once daily followed by 3 dummy infusions q6h infused over 60 (± 10) min to maintain the blind.
Drug: Daptomycin
Active Comparator: Vancomycin or nafcillin (or β-lactam equivalent)
IV vancomycin, 10 to 15 mg/kg, infused over 60 (± 10) minutes q6h (± 1 hour) or IV nafcillin (or β-lactam equivalent) at 100-200 mg/kg/day, in divided doses infused over 60 (± 10) min q6h (± 1 hour)
Drug: Vancomycin Drug: nafcillin

Detailed Description:

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 MRSA and MSSA. Daptomycin has proven clinical efficacy in adults in the treatment of 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.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

To be included in this study, participants must:

  • Obtain consent form;
  • 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 Data Monitoring Committee (DMC) review, enrollment will be broadened to 1-17 years.
  • Have diagnosis of acute hematogenous osteomyelitis (AHO) based on clinical, imaging and/or microbiological evidence as outlined below:

    • 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
    • Radiologic imaging (magnetic resonance imaging [MRI], bone scan, x-ray, or computed tomography [CT] scan) consistent with osteomyelitis
    • Microbiological evidence (gram stain, culture or PCR) from a bone biopsy or bone aspirate (if available), or blood
  • Laboratory evidence: CRP elevated, Erythrocyte sedimentation rate (ESR) elevated, leukocytosis or leukopenia, immature neutrophils
  • Have acute hematogenous osteomyelitis warranting IV antibacterial therapy initially as inpatient
  • 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.

Participants will not be allowed into the study if they:

  • Have documented history of any hypersensitivity or allergic reaction to daptomycin, vancomycin, or any β-lactam antibacterial agent
  • Have diagnosis of contiguous septic arthritis associated with osteomyelitis at baseline
  • Have acute hematogenous osteomyelitis that is located in the spine or pelvis or involving multiple locations (2 or more bones)
  • Have chronic osteomyelitis or symptoms of osteomyelitis exceeding 14 days
  • 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 any potentially effective intravenous antibacterial therapy for osteomyelitis within 96 hours before randomization unless 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01922011

Contacts
Contact: Claudia Abbes 781-860-8201 claudia.abbes@cubist.com

  Show 87 Study Locations
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Paula Bokesch, MD Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01922011     History of Changes
Other Study ID Numbers: DAP-PEDOST-11-03
Study First Received: August 9, 2013
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bone Diseases, Infectious
Osteomyelitis
Infection
Bone Diseases
Musculoskeletal Diseases
Nafcillin
Vancomycin
Daptomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014