Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006)

NCT01922011 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 3009-006DAP-PEDOST-11-032013-000864-28
• Study Type: interventional
• Target: 149
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Acute Hematogenous Osteomyelitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With 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.

  Clinical improvement was based on the Investigator's overall assessment of severity of each of the 3 general symptom categories of Pain, Inflammation, and Limb Function. Based on this evaluation, a participant was considered to have met criteria for clinical improvement according to the following definition: If 3 general categories are present at baseline: at least a 1-point improvement (i.e. severe to moderate, moderate to mild, mild to absent) in at least 2 of the general categories and no worsening in the other. If 2 general categories are present at baseline: at least a 2-point improvement (i.e. severe to mild, moderate to absent) in at least 1 of the general categories and no worsening or new findings in the others OR at least a 1-point improvement in both and no new findings in the other. If 1 general category is present at baseline: at least a 2-point improvement (i.e., severe to mild, moderate to absent) in that category and no new findings in the others.

  Up to study Day 5

Secondary Outcomes (5)

• Percentage of Participants With Clinical Improvement Measured as a Composite End Point of Pain, Inflammation, Limb Function, Body Temperature, and C-reactive Protein at End-of IV (EOIV) Therapy Visit.

  Up to study Day 5

• Percentage of Participants With a Favorable Clinical Outcome

  Baseline (within 48 hours prior to first dose of IV study drug) - and up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)

• Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure

  Baseline (within 48 hours prior to first dose of IV study drug) - and Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)

• Percentage of Participants With Sustained Clinical Improvement

  Baseline (within 48 hours prior to first dose of IV study drug) - up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)

• Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure

  Baseline (within 48 hours prior to first dose of IV study drug) - and Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)

Other Outcomes (8)

• Number of Participants With 1 or More Adverse Events (AEs)

  Administration of first dose up to approximately six and a half months after last dose of study drug

• Number of Participants With 1 or More Serious Adverse Events (SAEs)

  Administration of first dose through the last follow-up visit; an expected time of up to 6.5 months

• Concentration of Serum Creatine Kinase (CK)

  Baseline and End of Therapy IV (up to Day 42)

Study Arms (2)

Daptomycin

EXPERIMENTAL

Intravenous (IV) daptomycin was dosed as follows: age 12 years to \<18 years (7 mg/kg); age 7 years to \< 12 years (9 mg/kg); age 24 months to \<7 years (12 mg/kg); age 12 months to \<24 months (12 mg/kg). Drug was 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.

Drug: Daptomycin

Vancomycin or Nafcillin

ACTIVE COMPARATOR

IV vancomycin (or equivalent), 10 to 15 mg/kg, was infused over 60 (± 10) minutes q6h (± 1 hour) or IV nafcillin (or β-lactam equivalent) at 100-200 mg/kg/day, in divided doses was infused over 60 (± 10) min q6h (± 1 hour)

Drug: Vancomycin (or equivalent); Drug: Nafcillin (or equivalent)

Interventions

Daptomycin DRUG

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.

Daptomycin

Vancomycin (or equivalent) DRUG

IV vancomycin (or equivalent) (Infusions A,B,C,D), 10 to 15 mg/kg, infused over 60 (± 10) minutes q6h (± 1 hour)

Vancomycin or Nafcillin

Nafcillin (or equivalent) DRUG

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)

Vancomycin or Nafcillin

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Related Publications (1)

• Bradley JS, Arrieta AC, Digtyar VA, Popejoy MW, Grandhi A, Bokesch P, Hershberger E, Dorr MB, Tan CM, Murata Y, Wolf DJ, Bensaci M. Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis. Pediatr Infect Dis J. 2020 Sep;39(9):814-823. doi: 10.1097/INF.0000000000002790.

  PMID: 32639465 DERIVED

MeSH Terms

Interventions

Daptomycin; Vancomycin; Nafcillin

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Glycopeptides; Glycoconjugates; Carbohydrates; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2013
• First Posted: August 14, 2013
• Study Start: September 13, 2013
• Primary Completion: June 14, 2016
• Study Completion: December 20, 2016
• Last Updated: August 28, 2018
• Results First Posted: June 23, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share