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

NCT00428844 | Completed Phase 2 Results DMC

• 2 other identifiers: 3009-016DAP-OST-06-02
• Study Type: interventional
• Target: 75
• Locations: 3 countries
• Sites: 26

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.

Conditions

Osteomyelitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Safety - Notable Laboratory Abnormalities

  From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)

• Overall Clinical Outcome

  Approximately 6 weeks post last dose (approximately week 12)

• Microbiological Response

  Approximately 6 weeks post last dose (approximately week 12)

• Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)

  Day 4 (steady state)

• Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)

  Day 4 (steady state)

Study Arms (3)

Daptomycin 6 mg/kg

EXPERIMENTAL

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

Drug: daptomycin

Daptomycin 8 mg/kg

EXPERIMENTAL

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

Drug: daptomycin

Comparator

ACTIVE 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; Drug: teicoplanin; Drug: nafcillin; Drug: oxacillin; Drug: flucloxacillin

Interventions

daptomycin DRUG

6 mg/kg

Also known as: Cubicin

Daptomycin 6 mg/kg

vancomycin DRUG

1 gram

Also known as: Vancocin

Comparator

teicoplanin DRUG

6 mg/kg; used only at UK sites

Also known as: Targocid

Comparator

nafcillin DRUG

1-2 gram

Also known as: Unipen

Comparator

oxacillin DRUG

1-2 gram

Also known as: Bactocill

Comparator

flucloxacillin DRUG

1-2 mg

Also known as: Fluclox

Comparator

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (26)

UAMS College of Medicine

Little Rock, Arkansas, 72205-7199, United States

Location

South Denver Infectious Disease Associates, PC

Englewood, Colorado, 80133, United States

Location

Kane and Davis Associates

Washington D.C., District of Columbia, 20016, United States

Location

Infectious Disease Association of Tampa Bay

Tampa, Florida, 33606, United States

Location

Idaho Falls Infectious Diseases, PLLC

Idaho Falls, Idaho, 83404, United States

Location

Rush St. Luke's Medical Center

Chicago, Illinois, 60612, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62794, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Sierra Infectious Disease

Reno, Nevada, 89502, United States

Location

Dartmouth-Hitchcock Medical center

Lebanon, New Hampshire, 03756, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Summa Health Systems

Akron, Ohio, 44304, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Regional Infectious Diseases-Infusion Center

Lima, Ohio, 45801, United States

Location

Lehigh Valley Hospital Trauma and Critical Care Research

Allentown, Pennsylvania, 18103, United States

Location

Rothman Institute

Philadelphia, Pennsylvania, 19107, United States

Location

Gundersen Clinic, LTD

La Crosse, Wisconsin, 54601, United States

Location

Federal National Institution of Science "Russian Ilizarov Scientific Center" "Restorative Traumatology and Orthopedics" of Rosmedtechnology

Kurgan, 640014, Russia

Location

National Healthcare Institution of Moscow "City Clinical Hospital #64"

Moscow, 117292, Russia

Location

Federal Healthcare Institute "Novosibirsk Scientific Research Institute of Traumatology and Orthopedy Rosmeditechnology"

Novosibirsk, 630091, Russia

Location

National Educational Institution of Higher Professional Education "Saint Petersburg State Medical Academy n.a. Mechnikov of Roszdrav"

Saint Petersburg, 195067, Russia

Location

Russian Research Institute of Traumatology and Orthopedy

Saint Petersburg, 197046, Russia

Location

National Healthcare Institution "Samara Regional Clinical Hospital n.a. Kalinin"

Samara, 443095, Russia

Location

Nuffield Orthopaedics Centre, Bone Infection Unit

Headington, Oxford, Oxfordshire, OX37LD, United Kingdom

Location

The Royal Infirmary of Edinburgh at Little France

Edinburgh, Scotland, EH164SA, United Kingdom

Location

Brownlee Centre - Gartnavel General Hospital

Glasgow, Scotland, G120YN, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 22908174 DERIVED

MeSH Terms

Conditions

Osteomyelitis

Interventions

Daptomycin; Vancomycin; Teicoplanin; Nafcillin; Oxacillin; Floxacillin

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Ed Campanaro, VP Clinical Operations
• Organization: Cubist Pharmaceuticals, Inc.

ed.campanaro@cubist.com

781-860-8318

Study Officials

• Alistair Wheeler, MD

  Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2007
• First Posted: January 30, 2007
• Study Start: June 26, 2007
• Primary Completion: March 26, 2010
• Study Completion: June 23, 2010
• Last Updated: January 31, 2018
• Results First Posted: June 14, 2011

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

US (17); RU (6); GB (3)