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

Primary Purpose

Osteomyelitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
daptomycin
daptomycin
vancomycin
teicoplanin
nafcillin
oxacillin
flucloxacillin
Sponsored by
Cubist Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteomyelitis focused on measuring Osteomyelitis, Prosthetic Hip, Prosthetic Knee, MRSA, Osteomyelitis Associated with an Infected Prosthetic Hip or Knee Joint, Staphylococci

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UAMS College of Medicine
  • South Denver Infectious Disease Associates, PC
  • Kane and Davis Associates
  • Infectious Disease Association of Tampa Bay
  • Idaho Falls Infectious Diseases, PLLC
  • Rush St. Luke's Medical Center
  • Southern Illinois University School of Medicine
  • Mayo Clinic
  • Sierra Infectious Disease
  • Dartmouth-Hitchcock Medical center
  • Wake Forest University Health Sciences
  • Summa Health Systems
  • Cleveland Clinic
  • Regional Infectious Diseases-Infusion Center
  • Lehigh Valley Hospital Trauma and Critical Care Research
  • Rothman Institute
  • Gundersen Clinic, LTD
  • Federal National Institution of Science "Russian Ilizarov Scientific Center" "Restorative Traumatology and Orthopedics" of Rosmedtechnology
  • National Healthcare Institution of Moscow "City Clinical Hospital #64"
  • Federal Healthcare Institute "Novosibirsk Scientific Research Institute of Traumatology and Orthopedy Rosmeditechnology"
  • National Educational Institution of Higher Professional Education "Saint Petersburg State Medical Academy n.a. Mechnikov of Roszdrav"
  • Russian Research Institute of Traumatology and Orthopedy
  • National Healthcare Institution "Samara Regional Clinical Hospital n.a. Kalinin"
  • Nuffield Orthopaedics Centre, Bone Infection Unit
  • The Royal Infirmary of Edinburgh at Little France
  • Brownlee Centre - Gartnavel General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Daptomycin 6 mg/kg

Daptomycin 8 mg/kg

Comparator

Arm Description

Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).

Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).

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).

Outcomes

Primary Outcome Measures

Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
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
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
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
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)
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)
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.

Full Information

First Posted
January 26, 2007
Last Updated
January 7, 2018
Sponsor
Cubist Pharmaceuticals LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00428844
Brief Title
Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 26, 2007 (Actual)
Primary Completion Date
March 26, 2010 (Actual)
Study Completion Date
June 23, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cubist Pharmaceuticals LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteomyelitis
Keywords
Osteomyelitis, Prosthetic Hip, Prosthetic Knee, MRSA, Osteomyelitis Associated with an Infected Prosthetic Hip or Knee Joint, Staphylococci

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Daptomycin 6 mg/kg
Arm Type
Experimental
Arm Description
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
Arm Title
Daptomycin 8 mg/kg
Arm Type
Experimental
Arm Description
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
Arm Title
Comparator
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
daptomycin
Other Intervention Name(s)
Cubicin
Intervention Description
6 mg/kg
Intervention Type
Drug
Intervention Name(s)
daptomycin
Other Intervention Name(s)
Cubicin
Intervention Description
8 mg/kg
Intervention Type
Drug
Intervention Name(s)
vancomycin
Other Intervention Name(s)
Vancocin
Intervention Description
1 gram
Intervention Type
Drug
Intervention Name(s)
teicoplanin
Other Intervention Name(s)
Targocid
Intervention Description
6 mg/kg; used only at UK sites
Intervention Type
Drug
Intervention Name(s)
nafcillin
Other Intervention Name(s)
Unipen
Intervention Description
1-2 gram
Intervention Type
Drug
Intervention Name(s)
oxacillin
Other Intervention Name(s)
Bactocill
Intervention Description
1-2 gram
Intervention Type
Drug
Intervention Name(s)
flucloxacillin
Other Intervention Name(s)
Fluclox
Intervention Description
1-2 mg
Primary Outcome Measure Information:
Title
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Description
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.
Time Frame
From the 3rd day of therapy to 1 week post last dose (approximately week 7)
Secondary Outcome Measure Information:
Title
Safety - Notable Laboratory Abnormalities
Description
Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.
Time Frame
From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Title
Overall Clinical Outcome
Description
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.
Time Frame
Approximately 6 weeks post last dose (approximately week 12)
Title
Microbiological Response
Description
Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.
Time Frame
Approximately 6 weeks post last dose (approximately week 12)
Title
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)
Description
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.
Time Frame
Day 4 (steady state)
Title
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)
Description
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.
Time Frame
Day 4 (steady state)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alistair Wheeler, MD
Organizational Affiliation
Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA
Official's Role
Study Director
Facility Information:
Facility Name
UAMS College of Medicine
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205-7199
Country
United States
Facility Name
South Denver Infectious Disease Associates, PC
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80133
Country
United States
Facility Name
Kane and Davis Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016
Country
United States
Facility Name
Infectious Disease Association of Tampa Bay
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Idaho Falls Infectious Diseases, PLLC
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Rush St. Luke's Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62794
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Sierra Infectious Disease
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Dartmouth-Hitchcock Medical center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Summa Health Systems
City
Akron
State/Province
Ohio
ZIP/Postal Code
44304
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Regional Infectious Diseases-Infusion Center
City
Lima
State/Province
Ohio
ZIP/Postal Code
45801
Country
United States
Facility Name
Lehigh Valley Hospital Trauma and Critical Care Research
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
Rothman Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Gundersen Clinic, LTD
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
Federal National Institution of Science "Russian Ilizarov Scientific Center" "Restorative Traumatology and Orthopedics" of Rosmedtechnology
City
Kurgan
ZIP/Postal Code
640014
Country
Russian Federation
Facility Name
National Healthcare Institution of Moscow "City Clinical Hospital #64"
City
Moscow
ZIP/Postal Code
117292
Country
Russian Federation
Facility Name
Federal Healthcare Institute "Novosibirsk Scientific Research Institute of Traumatology and Orthopedy Rosmeditechnology"
City
Novosibirsk
ZIP/Postal Code
630091
Country
Russian Federation
Facility Name
National Educational Institution of Higher Professional Education "Saint Petersburg State Medical Academy n.a. Mechnikov of Roszdrav"
City
Saint Petersburg
ZIP/Postal Code
195067
Country
Russian Federation
Facility Name
Russian Research Institute of Traumatology and Orthopedy
City
Saint Petersburg
ZIP/Postal Code
197046
Country
Russian Federation
Facility Name
National Healthcare Institution "Samara Regional Clinical Hospital n.a. Kalinin"
City
Samara
ZIP/Postal Code
443095
Country
Russian Federation
Facility Name
Nuffield Orthopaedics Centre, Bone Infection Unit
City
Headington, Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX37LD
Country
United Kingdom
Facility Name
The Royal Infirmary of Edinburgh at Little France
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH164SA
Country
United Kingdom
Facility Name
Brownlee Centre - Gartnavel General Hospital
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G120YN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
22908174
Citation
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.
Results Reference
derived

Learn more about this trial

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

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