Clinical trial NCT05421312: Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
Official title: Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: PJI
Bone and Joint Infection
Pharmacokinetics
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Sint Maartenskliniek
First posted: 2022-06-16
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. Age 16 years or older.
2. 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).

Exclusion Criteria:

1. Antibiotic prophylaxis other than cefazolin 2000mg i.v.
2. Cefazolin use within 4 days previous to the reimplantation, other than the single dose administration of surgical prophylaxis just before incision.
3. Clindamycin loaded bone cement in situ.
4. BMI more than 35 kg/m2.

Primary outcomes:
measure: penetration cefazolin into synovial fluid
timeFrame: during surgical procedure prior to incision the synovial fluid sample will be taken
measure: penetration cefazolin into bone tissue
timeFrame: during surgical procedure prior to incision the synovial fluid sample will be taken
measure: penetration clindamycin into bone tissue
timeFrame: during surgical procedure, directly after opening the joint and before reimplantation of the prosthesis the bone samples will be taken
Secondary outcomes:
measure: AUC/MIC90 of cefazolin
timeFrame: sampling during procedure
measure: AUC/MIC90 of clindamycin
timeFrame: sampling during procedure
measure: factors associated with reduced cefazolin concentration
timeFrame: sampling during procedure
measure: factors associated with reduced clindamycin concentration
timeFrame: sampling during procedure
Other outcomes:
Locations:
Study officials:
affiliation: Radboud University Medical Center
name: Nynke Jager, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sint Maartenskliniek
name: Jon Goosen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: