Clinical trial NCT01757236: Efficacy and Safety Study of Antibiotic Treatment to Treat Hip Prosthetic Joint Infection
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hip Prosthetic Joint Infection
Keywords: Antibiotic
linezolid
linezolid/rifampin
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: Pfizer
name: International Clinical Trials Association
First posted: 2012-12-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Clinical cure rate
timeFrame: 12 months after the end of treatment
Secondary outcomes:
measure: Cure rate
timeFrame: 12 months after the end of treatment
measure: Cure rate
timeFrame: 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.
Other outcomes:
Locations:
city: Tours
country: France
facility: CHRU de Tours
state: Indre et Loire
city: Nantes
country: France
facility: CHU de Nantes
city: Poitiers
country: France
facility: CHU de Poitiers
city: Strasbourg
country: France
facility: Centre de Chirurgie Orthopédique et de la Main
city: Tourcoing
country: France
facility: CH de Tourcoing
city: Udine
country: Italy
facility: Azienda Opedaliera Universitaria San Maria della Misericordia
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
Study officials:
affiliation: CHRU de Tours FRANCE
name: Louis BERNARD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Nantes FRANCE
name: David BOUTOILLE
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Poitiers FRANCE
name: Gwenael LE MOAL
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Opedaliera Universitaria San Maria della Misericordia ITALY
name: Matteo BASSETTI
role: PRINCIPAL_INVESTIGATOR
affiliation: Facolta di Medicina e Chirugia ITALY
name: Silvano ESPOSITO
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre de Chirurgie Orthopédique et de la Main FRANCE
name: Jeannot GAUDIAS
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Barcelona SPAIN
name: Alex SORIANO
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Son Llatzer Palma Balears SPAIN
name: Bartolome LLADO FERRER
role: PRINCIPAL_INVESTIGATOR
affiliation: HGU Gregorio Maranon Madrid SPAIN
name: Mar SANCHEZ SOMOLINOS
role: PRINCIPAL_INVESTIGATOR
affiliation: CH de Tourcoing FRANCE
name: Eric SENNEVILLE
role: PRINCIPAL_INVESTIGATOR
References: