Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci - Full Text View

Purpose

This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.

Condition	Intervention	Phase
Osteomyelitis	Drug: daptomycin Drug: vancomycin Drug: teicoplanin Drug: nafcillin Drug: oxacillin Drug: flucloxacillin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Randomized Study Investigating the Safety, Efficacy and Pharmacokinetics of Daptomycin 6 mg/kg and 8 mg/kg Versus Comparator in the Treatment of Subjects Undergoing Surgical Standard of Care for Osteomyelitis Associated With an Infected Prosthetic Hip or Knee Joint Caused by Staphylococci

Resource links provided by NLM:

Drug Information available for: Oxacillin Nafcillin Nafcillin sodium Oxacillin sodium Vancomycin Vancomycin hydrochloride Daptomycin

Genetic and Rare Diseases Information Center resources: Osteomyelitis

U.S. FDA Resources

Further study details as provided by Cubist Pharmaceuticals LLC:

Primary Outcome Measures:

Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L) [ Time Frame: From the 3rd day of therapy to 1 week post last dose (approximately week 7) ] [ Designated as safety issue: Yes ]
Number of subjects with CPK >500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.

Secondary Outcome Measures:

Safety - Notable Laboratory Abnormalities [ Time Frame: From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30) ] [ Designated as safety issue: Yes ]
Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.
Overall Clinical Outcome [ Time Frame: Approximately 6 weeks post last dose (approximately week 12) ] [ Designated as safety issue: No ]
The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.
Microbiological Response [ Time Frame: Approximately 6 weeks post last dose (approximately week 12) ] [ Designated as safety issue: No ]
Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) [ Time Frame: Day 4 (steady state) ] [ Designated as safety issue: No ]
The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss) [ Time Frame: Day 4 (steady state) ] [ Designated as safety issue: No ]
The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.


Enrollment:	75
Study Start Date:	January 2007
Study Completion Date:	June 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Daptomycin 6 mg/kg Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).	Drug: daptomycin 6 mg/kg Other Name: Cubicin
Experimental: Daptomycin 8 mg/kg Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).	Drug: daptomycin 8 mg/kg Other Name: Cubicin
Active Comparator: Comparator Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).	Drug: vancomycin 1 gram Other Name: Vancocin Drug: teicoplanin 6 mg/kg; used only at UK sites Other Name: Targocid Drug: nafcillin 1-2 gram Other Name: Unipen Drug: oxacillin 1-2 gram Other Name: Bactocill Drug: flucloxacillin 1-2 mg Other Name: Fluclox

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject must be between the ages of 18 and 80, inclusive
Subject must have a diagnosis of prosthetic joint infection (PJI) in a hip or knee joint which has never previously been totally revised because of an infection and for which they are anticipated to undergo a two-stage replacement surgery
Subject must have a positive microbiological identifier of staphylococci.
If Subject is female of childbearing potential, must be willing to practice reliable birth control

Exclusion Criteria:

Subject has permanent intravascular prosthetic material such as heart valves or pacemakers
Subject has a creatinine clearance (CLCR) <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight.
Subject has significant hepatic dysfunction
Subject has a fungal or mycobacterial PJI
Subject is known to be HIV-infected with CD4 count ≤ 200 cells/ mm3
Subject has an abnormal creatine phosphokinase (CPK) (elevated CPK level ≥ 2x ULN) at baseline as measured by central laboratory
Subject is currently under treatment with chemotherapeutic agents excluding chronic maintenance therapy (e.g. tamoxifen to prevent relapse of primary breast cancer)
Subject is pregnant, nursing, or lactating.
Subject is receiving or is expected to receive chronic immunosuppressive therapy during the study.

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: NCT00428844

Show 26 Study Locations

Sponsors and Collaborators

Cubist Pharmaceuticals LLC

Investigators


Study Director:	Alistair Wheeler, MD	Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Byren I, Rege S, Campanaro E, Yankelev S, Anastasiou D, Kuropatkin G, Evans R. Randomized controlled trial of the safety and efficacy of Daptomycin versus standard-of-care therapy for management of patients with osteomyelitis associated with prosthetic devices undergoing two-stage revision arthroplasty. Antimicrob Agents Chemother. 2012 Nov;56(11):5626-32. doi: 10.1128/AAC.00038-12. Epub 2012 Aug 20.


Responsible Party:	Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier:	NCT00428844 History of Changes
Other Study ID Numbers:	3009-016 DAP-OST-06-02
Study First Received:	January 26, 2007
Results First Received:	March 16, 2011
Last Updated:	January 5, 2016
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals LLC:


Osteomyelitis Prosthetic Hip Prosthetic Knee	MRSA Osteomyelitis Associated with an Infected Prosthetic Hip or Knee Joint Staphylococci

Additional relevant MeSH terms:


Osteomyelitis Bone Diseases, Infectious Infection Bone Diseases Musculoskeletal Diseases Vancomycin Daptomycin	Floxacillin Oxacillin Teicoplanin Nafcillin Anti-Bacterial Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on September 23, 2016