Daptomycin With Rifampin for Treatment of Staphylococcal Prosthetic Joint Infection (Dapto-Studie)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by Centre Hospitalier Universitaire Vaudois
Sponsor:
Collaborators:
University of Lausanne Hospitals
Kantonsspital Liestal
Schulthess Klinik
Information provided by (Responsible Party):
Andrej Trampuz, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT01144000
First received: June 14, 2010
Last updated: June 24, 2012
Last verified: June 2012
  Purpose

To determine the outcome and safety of a combined antimicrobial treatment involving daptomycin and surgical approach involving retention or short-interval two-stage exchange of the implant. Patients with hip, knee and shoulder Prosthetic Joint Infection (PJI) caused by methicillin-susceptible and methicillin-resistant staphylococci will be included and followed during 2 years.


Condition Intervention Phase
Staphylococcal Infections
Drug: Daptomycin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Daptomycin (With or Without Rifampin) in the Treatment of Staphylococcal Hip, Knee and Shoulder Prosthetic Joint Infection

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • Treatment efficacy (infection-free period) [ Time Frame: During study and 2 years after ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of daptomycin (incidence of side effects) [ Time Frame: During study and 2 years after ] [ Designated as safety issue: Yes ]
  • Population pharmacokinetic profile of antibiotics (daptomycin, rifampin) will be evaluated through concentration measurements in plasma and drainage fluid. [ Time Frame: during treatment (12 weeks) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: June 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daptomycin
High dose Daptomycin in hip, knee and shoulder prosthesis infections
Drug: Daptomycin
10mg/kg/24h i.v.(intravenous) for 2-3 weeks with/or without rifampin (depending if the prosthesis is removed or not)
Other Name: Cubicin

Detailed Description:

In this prospective open observational clinical study (phase 2) patients with hip, knee and shoulder PJI (as defined below) caused by methicillin-susceptible and methicillin-resistant staphylococci will be included. An informed consent will be obtained prior to patient inclusion. Medical records will be prospectively abstracted for demographic characteristics, clinical, radiographic, laboratory and microbiologic data using a standardized case report form (CRF). After inclusion, intravenous daptomycin 10 mg/kg (calculated as actual body weight) is given once daily for 2-3 weeks, followed by oral rifampin-containing antibiotics for a total of 3 months (as outlined below).

Two surgical modalities will be applied according to the PJI treatment algorithm:

  • Open debridement and retention of the prosthesis (change of mobile parts): daptomycin will be combined with rifampin.
  • Two-stage exchange of the prosthesis with a short interval (2-3 weeks): daptomycin of the prosthesis: daptomycin will be used alone.

The decision whether the implant will be retained or removed is based on objective criteria of the treatment algorithm and is not subject to bias. All consecutive patients with a staphylococcal PJI infection of the hip, knee or shoulder prosthesis will be included, if no exclusion criterion is present, obviating the selection bias. Since not many specialized institutions are treating patients with PJI, we expect low number of patients.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent has been obtained;
  2. Subject is 18-80 years of age;
  3. Subject has a PJI of the hip, knee and shoulder prosthesis caused by Staphylococcus aureus or coagulase-negative staphylococci (CNS) susceptible to daptomycin and rifampin;
  4. Surgical approach: Debridement and retention of the prosthesis OR a two-stage prosthesis exchange with a short interval (2-3 weeks). The selection of the surgical procedure is performed according to the PJI treatment algorithm;
  5. Subject is willing to participate in the study, to follow protocol study treatment regimen, and to comply with all planned follow-up assessments;
  6. Females of childbearing potential are willing to practice reliable birth control measures other than oral contraceptives (e.g., condoms or diaphragms together with a spermicidal foam or gel) and willing to undergo a urine pregnancy test prior to study entry.

Exclusion Criteria:

  1. Significant renal insufficiency (creatinine clearance rate ≤30 ml/min, as determined by the Cockcroft-Gault equation at inclusion);
  2. Significant hepatic dysfunction at inclusion (AST or ALT ≥4 x upper limit of normal value);
  3. Elevated creatin phosphokinase (CPK) ≥2 x upper limit of normal value at inclusion
  4. PJI caused by additional microorganism;
  5. Non-adherence to the PJI treatment algorithm (see below);
  6. Subject has been previously enrolled in the study or is currently enrolled in another investigational study previously enrolled in the study or is currently enrolled in another investigational study, which deviates from the treatment algorithm;
  7. Subject had prior exposure to daptomycin within the past 3 months;
  8. Allergy or intolerance to daptomycin or rifampin, known hypersensitivity;
  9. Body mass index (BMI) >45 kg/m²;
  10. Subject is pregnant, nursing or lactating;
  11. Inability to read and understand the participant's information.
  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: NCT01144000

Contacts
Contact: Andrej Trampuz, MD +41 21 314 3992 andrej.trampuz@chuv.ch

Locations
Switzerland
Centre hospitaliere universitaire vaudois (CHUV) Not yet recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Andrej Trampuz    +41 (0)21 314 39 92    andrej.trampuz@chuv.ch   
Principal Investigator: Olivier Borens         
Kantonsspital Not yet recruiting
Liestal, Switzerland, 4410
Contact: Werner Zimmerli, MD    +41 61 925 1111    werner.zimmerli@ksli.ch   
Contact: Martin Clauss, MD       martin.clauss@ksli.ch   
Principal Investigator: Werner Zimmerli, MD         
Sub-Investigator: Martin Clauss, MD         
Schulhess Clinic Not yet recruiting
Zurich, Switzerland, 8008
Contact: Markus Vogt, MD       markus.vogt@zgks.ch   
Principal Investigator: Markus Vogt, MD         
Sponsors and Collaborators
Andrej Trampuz
University of Lausanne Hospitals
Kantonsspital Liestal
Schulthess Klinik
Investigators
Principal Investigator: Andrej Trampuz Centre hospitaliere universitaire vaudvoise (CHUV) University Hospital of Lausanne
  More Information

No publications provided

Responsible Party: Andrej Trampuz, Dr. med., Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT01144000     History of Changes
Other Study ID Numbers: CCBC134ACH03T
Study First Received: June 14, 2010
Last Updated: June 24, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Centre Hospitalier Universitaire Vaudois:
Prosthetic joint infection
daptomycin
staphylococcus

Additional relevant MeSH terms:
Staphylococcal Infections
Arthritis, Infectious
Gram-Positive Bacterial Infections
Bacterial Infections
Infection
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rifampin
Daptomycin
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 25, 2014