Hip Prosthetic Joint InfectionPhase 2LIZ-BONENCT01757236
Efficacy and Safety Study of Antibiotic Treatment to Treat Hip Prosthetic Joint Infection
A Phase 2 study testing VANCOMYCIN, CEFTRIAXONE and CLINDAMYCIN in people with Hip Prosthetic Joint Infection, run by University Hospital, Tours at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hip Prosthetic Joint Infection
- What is being tested?
- VANCOMYCIN, CEFTRIAXONE and CLINDAMYCIN
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 9 sitesin 3 countries
- Study dates
- Oct 2012to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
- Previous randomization in this protocol.
- Not expected or not likely to survive for the entire duration of the treatment period and TOC (12 months after the end of treatment).
- Hypersensitivity to the study drugs or their excipients.
- Identification of a pathogen resistant to the investigational drugs.
- Patients treated with a protease inhibitor(e.g. indinavir, ritonavir), or with delavirdine, or with nevirapine.
- 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,
- Patients with a degenerative neurological disease (Parkinson's disease, multiple sclerosis, Alzheimer's disease, etc.).
- 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.
- Patient who is participating or has participated in a clinical trial in the month prior to the study screening visit.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
France5 sites, 5 recruiting
- Recruiting
CHU de Nantes
Nantes
David BOUTOILLE
David BOUTOILLE
- Not yet recruiting
CHU de Poitiers
Poitiers
Gwenaël LE MOAL
Gwenaël LE MOAL
- Recruiting
Centre de Chirurgie Orthopédique et de la Main
Strasbourg, 67400
Jeannot GAUDIAS, Jeannot.GAUDIAS@chru-strasbourg.fr
Jeannot GAUDIAS
- Not yet recruiting
CH de Tourcoing
Tourcoing, 59208
Eric SENNEVILLE, esenneville@ch-tourcoing.fr
Eric SENNEVILLE
- Recruiting
CHRU de Tours
Tours, Indre et Loire, 37044
Louis BERNARD, +33 (0) 2 47 47 97 74, l.bernard@chu-tours.fr
Louis BERNARD
Spain3 sites, 3 recruiting
- Recruiting
Hospital Clinic of Barcelona
Barcelona, 08036
Alex SORIANO, ASORIANO@clinic.ub.es
Alex SORIANO
- Not yet recruiting
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Mar SANCHEZ SOMOLINOS
Mar SANCHEZ SOMOLINOS
- Not yet recruiting
Hospital Son Llatzer
Palma de Mallorca, 07198
Bartolome LLADO FERRER
Bartolome LLADO FERRER
Italy1 site, 1 recruiting
- Recruiting
Azienda Opedaliera Universitaria San Maria della Misericordia
Udine, 33100
Matteo BASSETTI, mattba@tin.it
Matteo BASSETTI
About this study
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.
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
- Being tested
- VANCOMYCIN, CEFTRIAXONE, CLINDAMYCIN, SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE), FLUOROQUINOLONE
- Keywords
- Antibiotic, linezolid, linezolid/rifampin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VANCOMYCINDrug
Also called VANCOCIN
CEFTRIAXONEDrug
Also called ROCEPHIN
CLINDAMYCINDrug
Also called DALACIN
SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE)Drug
Also called BACTRIM
FLUOROQUINOLONEDrug
Also called OFLOCIN
LINEZOLIDDrug
Also called ZYVOXID
RIFAMPINDrug
Also called RIFADIN
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: VANCOMYCIN; Drug: CEFTRIAXONE; Drug: LINEZOLID; Drug: RIFAMPIN |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months after the end of treatment
Secondary outcomes (2)
Cure rate
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.
Measured: 12 months after the end of treatment
Cure rate
Patients will be declared cured if clinical, radiological, and laboratory signs of infection normalized.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2012 (estimated)
- Study startOct 2012
- Primary completionApr 2016 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hip Prosthetic Joint InfectionStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, International Clinical Trials Association
- Responsible party
- Sponsor
- Investigators
- Louis BERNARD, Principal investigator, CHRU de Tours FRANCEDavid BOUTOILLE, Principal investigator, CHU de Nantes FRANCEGwenael LE MOAL, Principal investigator, CHU de Poitiers FRANCEMatteo BASSETTI, Principal investigator, Azienda Opedaliera Universitaria San Maria della Misericordia ITALYSilvano ESPOSITO, Principal investigator, Facolta di Medicina e Chirugia ITALYJeannot GAUDIAS, Principal investigator, Centre de Chirurgie Orthopédique et de la Main FRANCEAlex SORIANO, Principal investigator, Hospital Clinic of Barcelona SPAINBartolome LLADO FERRER, Principal investigator, Hospital Son Llatzer Palma Balears SPAIN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01757236
- Sponsor's protocol ID
- PHAO2011/LB/LIZ-BONE
- Other IDs
- 2012-000781-38
- Acronym
- LIZ-BONE
- Status last verified
- May 2014
- First submitted
- 20 Dec 2012
- Last updated
- 28 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01757236
- Acronym / sponsor ID
- LIZ-BONE / PHAO2011/LB/LIZ-BONE
- Conditions
- Hip Prosthetic Joint Infection
- Keywords
- Antibiotic, linezolid, linezolid/rifampin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Collaborators
- Pfizer, International Clinical Trials Association
- Study start
- Oct 2012
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 28 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Active comparator | Drug: VANCOMYCIN, Drug: CEFTRIAXONE, Drug: CLINDAMYCIN, Drug: SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE), Drug: FLUOROQUINOLONE, Drug: RIFAMPINIV 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. |
| Treatment B | Experimental | Drug: VANCOMYCIN, Drug: CEFTRIAXONE, Drug: LINEZOLID, Drug: RIFAMPINIV 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. |
| Treatment C | Experimental | Drug: VANCOMYCIN, Drug: CEFTRIAXONE, Drug: LINEZOLID, Drug: RIFAMPINIV 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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.
Key exclusion criteria (24 listed)
- Concerning women of childbearing age:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VANCOMYCINAlso: VANCOCIN | Drug | Treatment A, Treatment B, Treatment C |
| CEFTRIAXONEAlso: ROCEPHIN | Drug | Treatment A, Treatment B, Treatment C |
| CLINDAMYCINAlso: DALACIN | Drug | Treatment A |
| SULFAMETHOXAZOLE AND TRIMETHOPRIM (CO-TRIMOXAZOLE)Also: BACTRIM | Drug | Treatment A |
| FLUOROQUINOLONEAlso: OFLOCIN | Drug | Treatment A |
| LINEZOLIDAlso: ZYVOXID | Drug | Treatment B, Treatment C |
| RIFAMPINAlso: RIFADIN | Drug | Treatment A, Treatment B, Treatment C |
Primary outcome
Clinical cure rate
Time frame: 12 months after the end of treatment
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.
2 secondary outcomes
Cure rate
Time frame: 12 months after the end of treatment
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louis BERNARD principal investigator
CHRU de Tours FRANCE
David BOUTOILLE principal investigator
CHU de Nantes FRANCE
Gwenael LE MOAL principal investigator
CHU de Poitiers FRANCE
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VANCOMYCIN, CEFTRIAXONE and CLINDAMYCIN in people with Hip Prosthetic Joint Infection, run by University Hospital, Tours at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Louis BERNARD (+ 33 (0) 2 47 47 97 74 ext. 79774, l.bernard@chu-tours.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical cure rate (time frame: 12 months after the end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2014.