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

NCT ID: NCT01757236

Last Updated: 2014-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2016-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Hip Prosthetic Joint Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

VANCOMYCIN

Intervention Type DRUG

CEFTRIAXONE

Intervention Type DRUG

CLINDAMYCIN

Intervention Type DRUG

SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE)

Intervention Type DRUG

FLUOROQUINOLONE

Intervention Type DRUG

RIFAMPIN

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

VANCOMYCIN

Intervention Type DRUG

CEFTRIAXONE

Intervention Type DRUG

LINEZOLID

Intervention Type DRUG

RIFAMPIN

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

VANCOMYCIN

Intervention Type DRUG

CEFTRIAXONE

Intervention Type DRUG

LINEZOLID

Intervention Type DRUG

RIFAMPIN

Intervention Type DRUG

Interventions

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VANCOMYCIN

Intervention Type DRUG

CEFTRIAXONE

Intervention Type DRUG

CLINDAMYCIN

Intervention Type DRUG

SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE)

Intervention Type DRUG

FLUOROQUINOLONE

Intervention Type DRUG

LINEZOLID

Intervention Type DRUG

RIFAMPIN

Intervention Type DRUG

Other Intervention Names

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VANCOCIN ROCEPHIN DALACIN BACTRIM OFLOCIN ZYVOXID RIFADIN

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

International Clinical Trials Association

OTHER

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Louis BERNARD

Role: PRINCIPAL_INVESTIGATOR

CHRU de Tours FRANCE

David BOUTOILLE

Role: PRINCIPAL_INVESTIGATOR

CHU de Nantes FRANCE

Gwenael LE MOAL

Role: PRINCIPAL_INVESTIGATOR

CHU de Poitiers FRANCE

Matteo BASSETTI

Role: PRINCIPAL_INVESTIGATOR

Azienda Opedaliera Universitaria San Maria della Misericordia ITALY

Silvano ESPOSITO

Role: PRINCIPAL_INVESTIGATOR

Facolta di Medicina e Chirugia ITALY

Jeannot GAUDIAS

Role: PRINCIPAL_INVESTIGATOR

Centre de Chirurgie Orthopédique et de la Main FRANCE

Alex SORIANO

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona SPAIN

Bartolome LLADO FERRER

Role: PRINCIPAL_INVESTIGATOR

Hospital Son Llatzer Palma Balears SPAIN

Mar SANCHEZ SOMOLINOS

Role: PRINCIPAL_INVESTIGATOR

HGU Gregorio Maranon Madrid SPAIN

Eric SENNEVILLE

Role: PRINCIPAL_INVESTIGATOR

CH de Tourcoing FRANCE

Locations

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CHRU de Tours

Tours, Indre et Loire, France

Site Status RECRUITING

CHU de Nantes

Nantes, , France

Site Status RECRUITING

CHU de Poitiers

Poitiers, , France

Site Status NOT_YET_RECRUITING

Centre de Chirurgie Orthopédique et de la Main

Strasbourg, , France

Site Status RECRUITING

CH de Tourcoing

Tourcoing, , France

Site Status NOT_YET_RECRUITING

Azienda Opedaliera Universitaria San Maria della Misericordia

Udine, , Italy

Site Status RECRUITING

Hospital Clinic of Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Hospital Son Llatzer

Palma de Mallorca, , Spain

Site Status NOT_YET_RECRUITING

Countries

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France Italy Spain

Central Contacts

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Louis BERNARD

Role: CONTACT

+ 33 (0) 2 47 47 97 74 ext. 79774

Facility Contacts

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Louis BERNARD

Role: primary

+33 (0) 2 47 47 97 74

David BOUTOILLE

Role: primary

Gwenaël LE MOAL

Role: primary

Jeannot GAUDIAS

Role: primary

Eric SENNEVILLE

Role: primary

Matteo BASSETTI

Role: primary

Alex SORIANO

Role: primary

Mar SANCHEZ SOMOLINOS

Role: primary

Bartolome LLADO FERRER

Role: primary

Other Identifiers

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2012-000781-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PHAO2011/LB/LIZ-BONE

Identifier Type: -

Identifier Source: org_study_id

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