Efficacy and Safety Study of Antibiotic Treatment to Treat Hip Prosthetic Joint Infection

NCT01757236 | Unknown Phase 2 DMC

• 2 other identifiers: PHAO2011/LB/LIZ-BONE2012-000781-38
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 9

Brief Summary

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.

Conditions

Hip Prosthetic Joint Infection

Keywords

Antibiotic; linezolid; linezolid/rifampin

Outcome Measures

Primary Outcomes (1)

• Clinical cure rate

  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.

  12 months after the end of treatment

Secondary Outcomes (2)

• Cure rate

  12 months after the end of treatment

• Cure rate

  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.

Study Arms (3)

Treatment A

ACTIVE COMPARATOR

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; Drug: CEFTRIAXONE; Drug: CLINDAMYCIN; Drug: SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE); Drug: FLUOROQUINOLONE; Drug: RIFAMPIN

Treatment B

EXPERIMENTAL

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; Drug: CEFTRIAXONE; Drug: LINEZOLID; Drug: RIFAMPIN

Treatment C

EXPERIMENTAL

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; Drug: CEFTRIAXONE; Drug: LINEZOLID; Drug: RIFAMPIN

Interventions

VANCOMYCIN DRUG

Also known as: VANCOCIN

Treatment A; Treatment B; Treatment C

CEFTRIAXONE DRUG

Also known as: ROCEPHIN

Treatment A; Treatment B; Treatment C

CLINDAMYCIN DRUG

Also known as: DALACIN

Treatment A

SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE) DRUG

Also known as: BACTRIM

Treatment A

FLUOROQUINOLONE DRUG

Also known as: OFLOCIN

Treatment A

LINEZOLID DRUG

Also known as: ZYVOXID

Treatment B; Treatment C

RIFAMPIN DRUG

Also known as: RIFADIN

Treatment A; Treatment B; Treatment C

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Joint pain
• Effusion
• Erythema and sensation of heat at the implant site
• Limited range of motion in the affected joint
• 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.
• 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.
• All patients must undergo 1-stage revision surgery.
• 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.
• Willing and able to comply with scheduled visits, up to 6 weeks of treatment with the study antibiotics, laboratory tests, and other study procedures.
• Patient entitled to Health System benefits or other such benefits

You may not qualify if:

• Concerning women of childbearing age:
• intake of oral contraceptives (estroprogestins and progestins)
• unability to use adequate mechanical contraceptive precautions
• a positive pregnancy test result within 72 hours prior to randomization
• pregnant, or are currently breastfeeding and unwilling to discontinue breastfeeding during therapy
• 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.
• Platelet count less than 100 ×103/mm3 at the time of the examination performed during the screening period.
• Hemoglobin \< 9 g/dL at the time of the examination performed during the screening period.
• Infection affecting several joints.
• Rheumatological disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.)
• Previously diagnosed immune function disease(s) (e.g., AIDS), neutropenia (neutrophils \< 1000/mm3).
• Alcoholism or substance abuse sufficient, in the investigator's judgment, to prevent treatment adherence to the study drug and/or follow-up.
• Patients currently in peritoneal dialysis or receiving another treatment for renal failure (e.g., hemofiltration, CVVH).
• 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.
• 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.

Sponsors & Collaborators

• University Hospital, Tours: lead
• Pfizer: collaborator
• International Clinical Trials Association: collaborator

Study Sites (9)

CHRU de Tours

Tours, Indre et Loire, 37044, France

RECRUITING

CHU de Nantes

Nantes, France

RECRUITING

CHU de Poitiers

Poitiers, France

NOT YET RECRUITING

Centre de Chirurgie Orthopédique et de la Main

Strasbourg, 67400, France

RECRUITING

CH de Tourcoing

Tourcoing, 59208, France

NOT YET RECRUITING

Azienda Opedaliera Universitaria San Maria della Misericordia

Udine, 33100, Italy

RECRUITING

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

NOT YET RECRUITING

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

NOT YET RECRUITING

MeSH Terms

Interventions

Vancomycin; Ceftriaxone; Clindamycin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Fluoroquinolones; Linezolid; Rifampin

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Glycosides; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Pyrimidines; Drug Combinations; Pharmaceutical Preparations; 4-Quinolones; Quinolones; Quinolines; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Louis BERNARD

CONTACT

+ 33 (0) 2 47 47 97 74; l.bernard@chu-tours.fr

Study Design

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

Study Record Dates

• First Submitted: December 20, 2012
• First Posted: December 28, 2012
• Study Start: October 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 28, 2014

Record last verified: 2014-05

Locations

FR (5); IT (1); ES (3)