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

Osteomyelitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00428844
• Other study ID #: 3009-016
• Secondary ID: DAP-OST-06-02
• Status: Completed
• Phase: Phase 2
• First received: January 26, 2007
• Last updated: January 7, 2018
• Start date: June 26, 2007
• Est. completion date: June 23, 2010

Study information

• Verified date: January 2018
• Source: Cubist Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: June 23, 2010
• Est. primary completion date: March 26, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteomyelitis

Intervention

Drug:
• daptomycin
6 mg/kg
• daptomycin
8 mg/kg
• vancomycin
1 gram
• teicoplanin
6 mg/kg; used only at UK sites
• nafcillin
1-2 gram
• oxacillin
1-2 gram
• flucloxacillin
1-2 mg

Locations

Country	Name	City	State
Russian Federation	Federal National Institution of Science "Russian Ilizarov Scientific Center" "Restorative Traumatology and Orthopedics" of Rosmedtechnology	Kurgan
Russian Federation	National Healthcare Institution of Moscow "City Clinical Hospital #64"	Moscow
Russian Federation	Federal Healthcare Institute "Novosibirsk Scientific Research Institute of Traumatology and Orthopedy Rosmeditechnology"	Novosibirsk
Russian Federation	National Educational Institution of Higher Professional Education "Saint Petersburg State Medical Academy n.a. Mechnikov of Roszdrav"	Saint Petersburg
Russian Federation	Russian Research Institute of Traumatology and Orthopedy	Saint Petersburg
Russian Federation	National Healthcare Institution "Samara Regional Clinical Hospital n.a. Kalinin"	Samara
United Kingdom	The Royal Infirmary of Edinburgh at Little France	Edinburgh	Scotland
United Kingdom	Brownlee Centre - Gartnavel General Hospital	Glasgow	Scotland
United Kingdom	Nuffield Orthopaedics Centre, Bone Infection Unit	Headington, Oxford	Oxfordshire
United States	Summa Health Systems	Akron	Ohio
United States	Lehigh Valley Hospital Trauma and Critical Care Research	Allentown	Pennsylvania
United States	Rush St. Luke's Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	South Denver Infectious Disease Associates, PC	Englewood	Colorado
United States	Idaho Falls Infectious Diseases, PLLC	Idaho Falls	Idaho
United States	Gundersen Clinic, LTD	La Crosse	Wisconsin
United States	Dartmouth-Hitchcock Medical center	Lebanon	New Hampshire
United States	Regional Infectious Diseases-Infusion Center	Lima	Ohio
United States	UAMS College of Medicine	Little Rock	Arkansas
United States	Rothman Institute	Philadelphia	Pennsylvania
United States	Sierra Infectious Disease	Reno	Nevada
United States	Mayo Clinic	Rochester	Minnesota
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Infectious Disease Association of Tampa Bay	Tampa	Florida
United States	Kane and Davis Associates	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Cubist Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the 3rd day of therapy to 1 week post last dose (approximately week 7)
Secondary	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.	From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Secondary	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.	Approximately 6 weeks post last dose (approximately week 12)
Secondary	Microbiological Response	Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.	Approximately 6 weeks post last dose (approximately week 12)
Secondary	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.	Day 4 (steady state)
Secondary	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.	Day 4 (steady state)