PJIPhase 4CONCENTRATENCT05421312
Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
A Phase 4 study testing sampling blood, Sampling synovial fluid and Sampling bone tissue in people with PJI and Bone and Joint Infection, run by Radboud University Medical Center.
Trial summary
To prevent periprosthetic joint infection (PJI), optimal penetration of antibiotics into the joint-space is needed. In revision arthroplasty, the incidence of PJI is increased compared to primary arthroplasty. In this study, the penetration of antibiotic agents into the synovial fluid and bone will be analyzed. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- PJI, Bone and Joint Infection, Pharmacokinetics
- What is being tested?
- sampling blood, Sampling synovial fluid and Sampling bone tissue
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Sep 2022to Dec 2023
- Phase
- Phase 4
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years or older.
- Scheduled second stage revision arthroplasty (reimplantation) of the hip prosthesis during clindamycin 600mg three times a day orally for PJI, started at least 3 days before reimplantation (steady state).
Who cannot join
- Antibiotic prophylaxis other than cefazolin 2000mg i.v.
- Cefazolin use within 4 days previous to the reimplantation, other than the single dose administration of surgical prophylaxis just before incision.
- Clindamycin loaded bone cement in situ.
- BMI more than 35 kg/m2.
Trial locations and contacts
No sites are listed yet.
About this study
To prevent periprosthetic joint infection (PJI), optimal penetration of antibiotics into the joint-space is needed. In revision arthroplasty, the incidence of PJI is increased compared to primary arthroplasty. In this study, the penetration of antibiotic agents into the synovial fluid and bone will be analyzed. The concentration of antibiotics will be related tot the to the susceptibility (minimal inhibitory concentration; MIC-90) of microorganisms that frequently cause PJI.
Read the detailed description
Periprosthetic joint infection (PJI) is a feared complication of joint replacement, with an incidence of 0.5-1% after primary joint replacement and 3-5% after revision arthroplasty. For orthopaedic surgery involving a prosthesis, the administration of systemic antibiotic prophylaxis is strongly recommended to prevent PJI. Cefazolin is widely used as agent of choice in surgical antibiotic prophylaxis. Previous studies, all performed in patients undergoing primary joint replacement, demonstrated that the concentration of cefazolin in bone and synovial fluid was dose-dependent and exceeds the MIC90 for methicillin susceptible Staphylococcus aureus (MSSA), when given as 1 to 4 gram single dose shortly before incision. When a PJI is already present, clindamycin is used as treatment option in PJI caused by staphylococci (when combined with rifampicin) or cutibacteria. A limited number of studies have been performed to analyse the penetration of clindamycin into bone. These studies showed that clindamycin penetrates well into the bone and concentrations exceeded the MIC90 for MSSA. No studies have been performed to analyse the penetration of antibiotic agents into the periarticular tissue in patients who will undergo revision arthroplasty. In revision arthroplasty a foreign body (prosthesis) is in situ and periarticular tissue condition can be compromised due to previous surgical procedures and the presence of bone reaction to the prosthesis. It is not known whether the difference in PJI incidence after primary and revision arthroplasty may be explained by different penetration of the surgical antibiotic prophylaxis. The aim of this explorative study is to analyse the penetration of cefazolin and clindamycin into synovial fluid and bone and whether the concentration of the agents exceeds the MIC90 for micro-organisms frequently causing PJI.
- Conditions
- PJI, Bone and Joint Infection, Pharmacokinetics
- Being tested
- sampling blood, Sampling synovial fluid, Sampling bone tissue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sampling bloodDrug
During the reimplantation, 3 serum samples will be taken at different timepoint during the procedure.
Sampling synovial fluidDrug
During the reimplantation 1 synovial fluid sample will be taken prior to incision.
Sampling bone tissueDrug
During the reimplantation 2 cortical bone samples will be taken at different timepoints during the procedure.
| Study group | Role | What they receive |
|---|---|---|
| cefazolin | Other | The cefazolin antimicrobial prophylaxis (2000mg single dose intravenously 15-60 minutes before incision) is part of standard of care. Receives: Drug: sampling blood; Drug: Sampling synovial fluid; Drug: Sampling bone tissue |
| Clindamycin | Other | The clindamycin (600mg three times daily orally) PJI therapy is part of standard care. Receives: Drug: sampling blood; Drug: Sampling synovial fluid; Drug: Sampling bone tissue |
What is being measured
The primary outcome is the main question the study is designed to answer.
penetration cefazolin into synovial fluid
The ratio (%) of the concentration of cefazolin in synovial fluid to serum.
Measured: during surgical procedure prior to incision the synovial fluid sample will be taken
penetration cefazolin into bone tissue
The ratio (%) of the concentration of cefazolin in synovial fluid to serum.
Measured: during surgical procedure prior to incision the synovial fluid sample will be taken
penetration clindamycin into bone tissue
The ratio (%) of the concentration of cefazolin in bone tissue to serum.
Measured: during surgical procedure, directly after opening the joint and before reimplantation of the prosthesis the bone samples will be taken
Secondary outcomes (4)
AUC/MIC90 of cefazolin
The ratio of area under the curve of cefazolin to the minimal inhibitory concentration-90 of microorganisms
Measured: sampling during procedure
AUC/MIC90 of clindamycin
The ratio of area under the curve of cefazolin to the minimal inhibitory concentration-90 of microorganisms
Measured: sampling during procedure
factors associated with reduced cefazolin concentration
univariable and multivariable (if possible) analysis for factors that are associated with reduced concentration of cefazolin (i.e., BMI, age, ..)
Measured: sampling during procedure
factors associated with reduced clindamycin concentration
univariable and multivariable (if possible) analysis for factors that are associated with reduced concentration of cefazolin (i.e., BMI, age, ..)
Measured: sampling during procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2022
- Study startSep 2022 (estimated)
- Primary completionSep 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PJIStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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 4
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This explorative, low intervention study will be conducted in the Radboudumc Nijmegen and Sint Maartenskliniek (SMK) Nijmegen, The Netherlands. Subject will receive the cefazolin antibiotic prophylaxis and clindamycin antibiotic therapy as standard of care. The study interventions will include blood sampling on baseline and perioperative sampling of serum, synovial fluid and bone for the concentration measurements of the antibiotic agents. For every participating subject 3 serum samples, 1 synovial fluid sample and 2 bone samples will be taken for concentration measurement of cefazolin and clindamycin. Samples will be taken at different timepoints during the procedure.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Sint Maartenskliniek
- Responsible party
- Sponsor
- Investigators
- Nynke Jager, PhD, Principal investigator, Radboud University Medical CenterJon Goosen, MD, PhD, Principal investigator, Sint Maartenskliniek
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05421312
- Sponsor's protocol ID
- 2022-13583
- Acronym
- CONCENTRATE
- Status last verified
- Jun 2022
- First submitted
- 7 Jun 2022
- Last updated
- 16 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
- ClinicalTrials.gov ID
- NCT05421312
- Acronym / sponsor ID
- CONCENTRATE / 2022-13583
- Conditions
- PJI, Bone and Joint Infection, Pharmacokinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Sint Maartenskliniek
- Study start
- Sep 2022 (estimated)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 16 Jun 2022 (actual)
- 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.
To prevent periprosthetic joint infection (PJI), optimal penetration of antibiotics into the joint-space is needed. In revision arthroplasty, the incidence of PJI is increased compared to primary arthroplasty. In this study, the penetration of antibiotic agents into the synovial fluid and bone will be analyzed. The concentration of antibiotics will be related tot the to the susceptibility (minimal inhibitory concentration; MIC-90) of microorganisms that frequently cause PJI.
Detailed description
Periprosthetic joint infection (PJI) is a feared complication of joint replacement, with an incidence of 0.5-1% after primary joint replacement and 3-5% after revision arthroplasty. For orthopaedic surgery involving a prosthesis, the administration of systemic antibiotic prophylaxis is strongly recommended to prevent PJI. Cefazolin is widely used as agent of choice in surgical antibiotic prophylaxis. Previous studies, all performed in patients undergoing primary joint replacement, demonstrated that the concentration of cefazolin in bone and synovial fluid was dose-dependent and exceeds the MIC90 for methicillin susceptible Staphylococcus aureus (MSSA), when given as 1 to 4 gram single dose shortly before incision. When a PJI is already present, clindamycin is used as treatment option in PJI caused by staphylococci (when combined with rifampicin) or cutibacteria. A limited number of studies have been performed to analyse the penetration of clindamycin into bone. These studies showed that clindamycin penetrates well into the bone and concentrations exceeded the MIC90 for MSSA. No studies have been performed to analyse the penetration of antibiotic agents into the periarticular tissue in patients who will undergo revision arthroplasty. In revision arthroplasty a foreign body (prosthesis) is in situ and periarticular tissue condition can be compromised due to previous surgical procedures and the presence of bone reaction to the prosthesis. It is not known whether the difference in PJI incidence after primary and revision arthroplasty may be explained by different penetration of the surgical antibiotic prophylaxis. The aim of this explorative study is to analyse the penetration of cefazolin and clindamycin into synovial fluid and bone and whether the concentration of the agents exceeds the MIC90 for micro-organisms frequently causing PJI.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This explorative, low intervention study will be conducted in the Radboudumc Nijmegen and Sint Maartenskliniek (SMK) Nijmegen, The Netherlands. Subject will receive the cefazolin antibiotic prophylaxis and clindamycin antibiotic therapy as standard of care. The study interventions will include blood sampling on baseline and perioperative sampling of serum, synovial fluid and bone for the concentration measurements of the antibiotic agents. For every participating subject 3 serum samples, 1 synovial fluid sample and 2 bone samples will be taken for concentration measurement of cefazolin and clindamycin. Samples will be taken at different timepoints during the procedure.
| Arm | Type | Receives |
|---|---|---|
| cefazolin | Other | Drug: sampling blood, Drug: Sampling synovial fluid, Drug: Sampling bone tissueThe cefazolin antimicrobial prophylaxis (2000mg single dose intravenously 15-60 minutes before incision) is part of standard of care. |
| Clindamycin | Other | Drug: sampling blood, Drug: Sampling synovial fluid, Drug: Sampling bone tissueThe clindamycin (600mg three times daily orally) PJI therapy is part of standard care. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Age 16 years or older.
- Scheduled second stage revision arthroplasty (reimplantation) of the hip prosthesis during clindamycin 600mg three times a day orally for PJI, started at least 3 days before reimplantation (steady state).
Key exclusion criteria (4 listed)
- Antibiotic prophylaxis other than cefazolin 2000mg i.v.
- Cefazolin use within 4 days previous to the reimplantation, other than the single dose administration of surgical prophylaxis just before incision.
- Clindamycin loaded bone cement in situ.
- BMI more than 35 kg/m2.
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 |
|---|---|---|
| sampling bloodDuring the reimplantation, 3 serum samples will be taken at different timepoint during the procedure. | Drug | Clindamycin, cefazolin |
| Sampling synovial fluidDuring the reimplantation 1 synovial fluid sample will be taken prior to incision. | Drug | Clindamycin, cefazolin |
| Sampling bone tissueDuring the reimplantation 2 cortical bone samples will be taken at different timepoints during the procedure. | Drug | Clindamycin, cefazolin |
Primary outcome
penetration cefazolin into synovial fluid
Time frame: during surgical procedure prior to incision the synovial fluid sample will be taken
The ratio (%) of the concentration of cefazolin in synovial fluid to serum.
penetration cefazolin into bone tissue
Time frame: during surgical procedure prior to incision the synovial fluid sample will be taken
The ratio (%) of the concentration of cefazolin in synovial fluid to serum.
penetration clindamycin into bone tissue
Time frame: during surgical procedure, directly after opening the joint and before reimplantation of the prosthesis the bone samples will be taken
The ratio (%) of the concentration of cefazolin in bone tissue to serum.
4 secondary outcomes
AUC/MIC90 of cefazolin
Time frame: sampling during procedure
AUC/MIC90 of clindamycin
Time frame: sampling during procedure
factors associated with reduced cefazolin concentration
Time frame: sampling during procedure
factors associated with reduced clindamycin concentration
Time frame: sampling during procedure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2022.
- Individual participant dataSharing planned: No
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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.
Nynke Jager, PhD principal investigator
Radboud University Medical Center
Jon Goosen, MD, PhD principal investigator
Sint Maartenskliniek
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sampling blood, Sampling synovial fluid and Sampling bone tissue in people with PJI and Bone and Joint Infection, run by Radboud University Medical Center.
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 2 inclusion and 4 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 16 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Karin Veerman, MD (+31683845606, karin.veerman@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
penetration cefazolin into synovial fluid (time frame: during surgical procedure prior to incision the synovial fluid sample will be taken). The study lists 3 primary outcomes in all. 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 16 Jun 2022.