Efficacy and Safety Study of Antibiotic Treatment to Treat Hip Prosthetic Joint Infection (LIZ-BONE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital, Tours
Sponsor:
Collaborators:
Pfizer
International Clinical Trials Association
Information provided by (Responsible Party):
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT01757236
First received: December 20, 2012
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the efficacy of oral linezolid-rifampin combination therapy (over 4 or 6 weeks) versus the standard of care in the treatment of Gram-positive prosthetic hip joint infection with a one-stage surgical treatment.


Condition Intervention Phase
Hip Prosthetic Joint Infection
Drug: VANCOMYCIN
Drug: CEFTRIAXONE
Drug: CLINDAMYCIN
Drug: SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE)
Drug: FLUOROQUINOLONE
Drug: LINEZOLID
Drug: RIFAMPIN
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: Prospective,Randomized,Open Label,European Multicenter Study of the Efficacy of the Linezolid-rifampin Combination Versus Standard of Care in the Treatment of Gram-positive.

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • Clinical cure rate [ Time Frame: 12 months after the end of treatment ] [ Designated as safety issue: No ]
    Clinical cure rate in the modified intent-to-treat (mITT)population during the hospital visit. Patients will be declared cured if clinical signs of infection are normalized.


Secondary Outcome Measures:
  • Cure rate [ Time Frame: 12 months after the end of treatment ] [ Designated as safety issue: Yes ]
    Cure rate ine the modified intent-to-treat population during the hospital visit. Patients will be cdeclared cured if radiological and laboratory signs of infection are normalized.

  • Cure rate [ Time Frame: 6 and 24 months after the end of treatment for the modified intent-to-treat population and at 12 months for the per protocol population. ] [ Designated as safety issue: Yes ]
    Patients will be declared cured if clinical, radiological, and laboratory signs of infection normalized.


Estimated Enrollment: 100
Study Start Date: October 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment A

IV vancomycin (15mg/kg every 12 hours or in a continuous infusion) and IV ceftriaxone (2g daily) until Day 2 to 7 (until the susceptibility test results are obtained).

Patients with only a confirmed Gram-positive infection will continue the study and will receive standard of care antibiotic therapy including oral rifampin (10-15mg/kg every 12 hours) combined with either oral clindamycin (600 mg every 8 hours) or oral sulfamethoxazole and trimethoprim (800/160 mg every 8 hours) or oral fluoroquinolone (Ofloxacin 200 mg every 12 hours). The total duration of antibiotic therapy from the day of the surgical procedure until the end of treatment (EOT) will be 6 weeks.

Drug: VANCOMYCIN
Other Name: VANCOCIN
Drug: CEFTRIAXONE
Other Name: ROCEPHIN
Drug: CLINDAMYCIN
Other Name: DALACIN
Drug: SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE)
Other Name: BACTRIM
Drug: FLUOROQUINOLONE
Other Name: OFLOCIN
Drug: RIFAMPIN
Other Name: RIFADIN
Experimental: Treatment B

IV vancomycin (15mg/kg every 12 hours or in a continuous infusion) and IV ceftriaxone (2g daily) until Day 2 to 7 (until the susceptibility test results are obtained).

Patients with only a confirmed Gram-positive infection will continue the study and will receive oral linezolid (600mg every 12 hours) combined with oral rifampin (10-15mg/kg every 12 hours).

The total duration of antibiotic therapy from the day of the surgical procedure until the end of treatment (EOT) will be 6 weeks.

Drug: VANCOMYCIN
Other Name: VANCOCIN
Drug: CEFTRIAXONE
Other Name: ROCEPHIN
Drug: LINEZOLID
Other Name: ZYVOXID
Drug: RIFAMPIN
Other Name: RIFADIN
Experimental: Treatment C
IV linezolid (600 mg every 12 hours)and IV ceftriaxone (2g daily) until Day 2. Oral or IV rifampin (10-15 mg/kg every 12 hours) will be added 48 hours after initiating the study treatment. Treatment with the study drug will continue until Day 2 to 7 (until the susceptibility test results are obtained). Patients with only a confirmed Gram-positive infection will continue the study. Treatment with ceftriaxone will be discontinued and the patient will switch to oral linezolid and oral rifampin. The total duration of antibiotic therapy from the day of the surgical procedure until the end of treatment (EOT) will be 4 weeks.
Drug: VANCOMYCIN
Other Name: VANCOCIN
Drug: CEFTRIAXONE
Other Name: ROCEPHIN
Drug: LINEZOLID
Other Name: ZYVOXID
Drug: RIFAMPIN
Other Name: RIFADIN

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men or women ≥ 18 to ≤ 80 years of age, weight ≥ 40 kg, BMI < 35, who have received a diagnosis of chronic PJI (lasting more than 4 weeks but less than 24 months) requiring a one-stage surgical procedure and presenting at least ONE of the following clinical signs and symptoms:

    1. Joint pain
    2. Effusion
    3. Erythema and sensation of heat at the implant site
    4. Limited range of motion in the affected joint
  2. Intraoperative microbiological specimens: during the surgical resection, 5 separate surgical specimens (at least 3) must be sent for culture and susceptibility testing. These specimens must be taken from different locations such as: Hip capsule, femoral membrane, acetabular membrane, synovium, and synovial fluid with separate instruments. A minimum of 2 surgical specimens must be positive. If a preoperative puncture revealed the presence of an acceptable (Gram+) pathogen, it is acceptable if only one pathogen similar to the previously revealed one is identified during the surgical procedure.
  3. Documented presence of Gram-positive bacteria as sole pathogen responsible for the infection.

    Note: This criterion must be verified after obtaining the results of the susceptibility test performed on the specimens taken during the surgical procedure. The verification will occur between Day 2 and Day 7 of the study.

  4. All patients must undergo 1-stage revision surgery.
  5. IRB or IEC approved informed consent form signed and dated. Informed consent will be obtained from each patient before participation in this research study. If any patient is unable to give consent, it may be obtained from the patient's next of kin or legal representative in accordance with current laws and regulations.
  6. Willing and able to comply with scheduled visits, up to 6 weeks of treatment with the study antibiotics, laboratory tests, and other study procedures.
  7. Patient entitled to Health System benefits or other such benefits

Exclusion Criteria:

  1. Concerning women of childbearing age:

    1. intake of oral contraceptives (estroprogestins and progestins)
    2. unability to use adequate mechanical contraceptive precautions
    3. a positive pregnancy test result within 72 hours prior to randomization
    4. pregnant, or are currently breastfeeding and unwilling to discontinue breastfeeding during therapy
  2. Patients with a prosthetic joint infection caused by: Gram-negative, mixed Gram-negative and Gram-positive, fungal, or mycobacterial microorganisms. If a previous radiologically guided puncture has revealed the presence of a Gram-negative microorganism, the patient must not be enrolled in this study.
  3. Platelet count less than 100 ×103/mm3 at the time of the examination performed during the screening period.
  4. Hemoglobin < 9 g/dL at the time of the examination performed during the screening period.
  5. Infection affecting several joints.
  6. Rheumatological disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.)
  7. Previously diagnosed immune function disease(s) (e.g., AIDS), neutropenia (neutrophils < 1000/mm3).
  8. Alcoholism or substance abuse sufficient, in the investigator's judgment, to prevent treatment adherence to the study drug and/or follow-up.
  9. Patients currently in peritoneal dialysis or receiving another treatment for renal failure (e.g., hemofiltration, CVVH).
  10. Liver failure with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or total bilirubin levels upper or egal to 5 times the upper limit of normal.
  11. Patients with other concurrent serious infections such as: endocarditis, meningitis, or central nervous system (CNS) infections, decubitus and ischemic ulcers with underlying osteomyelitis, necrotizing fasciitis, gas gangrene. If suspected, these diagnoses must be ruled out prior to enrollment in the study.
  12. Previous randomization in this protocol.
  13. Not expected or not likely to survive for the entire duration of the treatment period and TOC (12 months after the end of treatment).
  14. Hypersensitivity to the study drugs or their excipients.
  15. Identification of a pathogen resistant to the investigational drugs.
  16. Patients treated with a protease inhibitor(e.g. indinavir, ritonavir), or with delavirdine, or with nevirapine.
  17. Patients treated or having been treated within two weeks prior surgery with an MAOI (A or B), an antiserotonergic drug, a tricyclic antidepressant, an agonist of 5HT1-receptor(triptan), a direct or indirect sympathomimetic drug (including adrenergic bronchodilator, pseudoephedrin, phenylpropanolamin), a vasopressor (adrenalin, noradrenalin), dopaminergic drug, pethidin or buspirone,
  18. Patients with a degenerative neurological disease (Parkinson's disease, multiple sclerosis, Alzheimer's disease, etc.).
  19. Patient presenting an uncontrolled hypertension, a pheochromocytoma, a carcinoid syndrome, a hyperthyroidism, a bipolar depression, a dysthymic schizophrenia, an acute confusional state, pophyria or a history of retrobulbar optic neuritis.
  20. Patient who is participating or has participated in a clinical trial in the month prior to the study screening visit.
  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: NCT01757236

Contacts
Contact: Louis BERNARD + 33 (0) 2 47 47 97 74 ext 79774 l.bernard@chu-tours.fr

Locations
France
CHRU de Tours Recruiting
Tours, Indre et Loire, France, 37044
Contact: Louis BERNARD    +33 (0) 2 47 47 97 74    l.bernard@chu-tours.fr   
Principal Investigator: Louis BERNARD         
CHU de Nantes Recruiting
Nantes, France
Contact: David BOUTOILLE         
Principal Investigator: David BOUTOILLE         
CHU de Poitiers Not yet recruiting
Poitiers, France
Contact: Gwenaël LE MOAL         
Principal Investigator: Gwenaël LE MOAL         
Centre de Chirurgie Orthopédique et de la Main Recruiting
Strasbourg, France, 67400
Contact: Jeannot GAUDIAS       Jeannot.GAUDIAS@chru-strasbourg.fr   
Principal Investigator: Jeannot GAUDIAS         
CH de Tourcoing Not yet recruiting
Tourcoing, France, 59208
Contact: Eric SENNEVILLE       esenneville@ch-tourcoing.fr   
Principal Investigator: Eric SENNEVILLE         
Italy
Azienda Opedaliera Universitaria San Maria della Misericordia Recruiting
Udine, Italy, 33100
Contact: Matteo BASSETTI       mattba@tin.it   
Principal Investigator: Matteo BASSETTI         
Spain
Hospital Clinic of Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Alex SORIANO       ASORIANO@clinic.ub.es   
Principal Investigator: Alex SORIANO         
Hospital General Universitario Gregorio Maranon Not yet recruiting
Madrid, Spain, 28007
Contact: Mar SANCHEZ SOMOLINOS         
Principal Investigator: Mar SANCHEZ SOMOLINOS         
Hospital Son Llatzer Not yet recruiting
Palma de Mallorca, Spain, 07198
Contact: Bartolome LLADO FERRER         
Principal Investigator: Bartolome LLADO FERRER         
Sponsors and Collaborators
University Hospital, Tours
Pfizer
International Clinical Trials Association
Investigators
Principal Investigator: Louis BERNARD CHRU de Tours FRANCE
Principal Investigator: David BOUTOILLE CHU de Nantes FRANCE
Principal Investigator: Gwenael LE MOAL CHU de Poitiers FRANCE
Principal Investigator: Matteo BASSETTI Azienda Opedaliera Universitaria San Maria della Misericordia ITALY
Principal Investigator: Silvano ESPOSITO Facolta di Medicina e Chirugia ITALY
Principal Investigator: Jeannot GAUDIAS Centre de Chirurgie Orthopédique et de la Main FRANCE
Principal Investigator: Alex SORIANO Hospital Clinic of Barcelona SPAIN
Principal Investigator: Bartolome LLADO FERRER Hospital Son Llatzer Palma Balears SPAIN
Principal Investigator: Mar SANCHEZ SOMOLINOS HGU Gregorio Maranon Madrid SPAIN
Principal Investigator: Eric SENNEVILLE CH de Tourcoing FRANCE
  More Information

No publications provided

Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT01757236     History of Changes
Other Study ID Numbers: PHAO2011/LB/LIZ-BONE, 2012-000781-38
Study First Received: December 20, 2012
Last Updated: May 27, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by University Hospital, Tours:
Antibiotic
linezolid
linezolid/rifampin

Additional relevant MeSH terms:
Arthritis, Infectious
Infection
Arthritis
Joint Diseases
Musculoskeletal Diseases
Anti-Bacterial Agents
Ceftriaxone
Clindamycin
Clindamycin-2-phosphate
Rifampin
Vancomycin
Fluoroquinolones
Antibiotics, Antitubercular
Linezolid
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents

ClinicalTrials.gov processed this record on July 20, 2014