A Phase 4 interventional study of Clindamycin and Rifampicin and levofloxacin in Prosthetic-joint Infection, Infection Hip and Infection; Knee, Joint, sponsored by Leiden University Medical Center. Recruiting at 13 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-12-15.
Sponsored by Leiden University Medical Center · Phase 4, Interventional, and Treatment
In this Dutch multicenter clinical trial, patients with a staphylococcal prosthetic joint infection, will, in the oral antibiotic treatment phase, be randomized between clindamycin monotherapy and rifampicin / levofloxacin combination therapy. The clinical endpoint will be treatment success one year after finishing antimicrobial treatment.
This is a pragmatic, multicenter, randomized controlled open label trial with a non-inferiority design, comparing the efficacy of rifampicin-based combination antimicrobial therapy versus antimicrobial monotherapy with clindamycin during the oral treatment phase of prosthetic joint infection caused by Staphylococcus spp. The total duration of follow-up will be 15 months from the initial DAIR.
All adult patients, aged 18 years or older, diagnosed and hospitalized with hip- or knee PJI caused by Staphylococcus spp and treated by the DAIR strategy (see Interventions), are eligible for inclusion. The diagnosis of PJI is defined according to the EBJIS 2021 criteria. Exclusion criteria are a contra-indication for rifampicin (due to a resistant strain, a proven allergic reaction, difficult drug-drug-interactions or other contra-indications as listed in the SmPC's of the antibiotics), a contra-indication for levofloxacin and clindamycin and cotrimoxazole and tetracyclines (due to a resistant strain, a proven allergic reaction, difficult drug-drug-interactions or other contra-indications as listed in the SmPC's of the antibiotics), (iii)complicated S. aureus bacteremia or concurrent endocarditis requiring long-term iv antibiotic treatment > 3 weeks , (iv) an infection for which there are no suitable antibiotic choices to permit randomization between the two arms of the trial (for instance, where organisms are only sensitive to intravenous antibiotics), (v) treatment failure before the start of oral therapy, (vi) more than two separate surgical debridements , (vii)an unsatisfactory response to initial treatment leading to continuation of intravenous therapy beyond day 21, (viii) patients with an expected life expectancy \<12 months, (ix) patients with a tumor prosthesis , (x) patients receiving chemotherapy for active malignancy in the next 12 months, (xi) patients who are scheduled in advance for chronic suppressive antibiotic therapy after the initial 12 weeks of antibiotic treatment, (xii) The patient is unlikely to comply with trial requirements following randomization in the opinion of the investigator, (xiii) Pregnancy or breastfeeding, (xiv) Patients who are not able to read or communicate in Dutch or English will be excluded from participating in this study.
The main trial endpoint is treatment success 15 months after DAIR (=1 year after finishing antibiotic treatment). Treatment success will be defined as absence of all of the following:
(I) Infection related re-surgery of the initially affected prosthetic joint (II) New antibiotic treatment for suspected or proven infection of the index joint.
(III) Ongoing use of antibiotics for the index joint at the end of follow-up. (IV) Death
Secondary outcomes are (a) Quality of life, measured with the 5-level EQ-5D version (EQ-5D-5L) questionnaires. The EQ-5D-5L is a standardized and validated measure of health status developed by the EuroQol Group to provide a comprehensive generic measure of health for clinical and economic appraisal. This 'quality of life' questionnaire will be scored at the time of randomization, at week 6 after the initial surgical debridement and after 3 months.
(b) Adverse events. The number of SAEs during antimicrobial treatment and follow up ii. The number of switches to a different oral regimen, iii. The number of antibiotic associated AEs (classified by the modified Hartwig and Siegel scale). (c) The number of patients developing Clostridioides difficile infection during treatment. (d) The occurrence of rifampicin resistance in bacteria in patients with a microbiologically confirmed failure of treatment.
6,687 studies on the registry are indexed under Infections; 807 are open to participants now.
This study's planned enrollment of 316 is above the median of 120 across 4,200 interventional studies indexed under Infections.
Browse Infections studies →Leiden University Medical Center is the lead sponsor of 326 studies on the registry; 106 are open to participants now.
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Exclusion Criteria:
(i) a contra-indication for rifampicin (e.g. a resistant strain or proven allergic reaction or difficult drug-drug-interactions) (ii) complicated S. aureus bacteremia or concurrent endocarditis requiring long-term iv antibiotic treatment > 2 weeks (iii) An infection for which there are no suitable antibiotic choices to permit Randomization between the two arms of the trial (for instance, where organisms are only sensitive to intravenous antibiotics) (iv) treatment failure before the start of oral therapy, (v) an unsatisfactory response to initial treatment leading to continuation of intravenous therapy beyond day 21, (vi) patients with an expected life expectancy \<12 months, (vii) patients with a tumor prosthesis (viii) patients receiving chemotherapy for active malignancy in the next 12 months (ix) patients who are scheduled in advance for chronic suppressive antibiotic therapy for >12 months, (x) The patient is unlikely to comply with trial requirements following Randomization in the opinion of the investigator (xi) Pregnancy (xii) Patients who are not able to read or communicate in Dutch or English will be excluded from participating in this study
rifampicin 450mg BID + levofloxacin 500mg BID in the oral treatment phase with a total duration of antibiotics of 12 weeks
Drug: Rifampicin and levofloxacin
clindamycin 600mg TID in the oral treatment phase with a total duration of antibiotics of 12 weeks
Drug: Clindamycin
antimicrobial treatment in oral treatment phase of staphylococcal prosthetic joint infection
antimicrobial treatment in oral treatment phase of staphylococcal prosthetic joint infection
treatment success
Proportion of patients with treatment success 15 months after DAIR (=1 year after finishing antibiotic) in both randomised groups treatment). Treatment success will be defined as absence of all of the following: (I) Infection related re-surgery of the initially affected prosthetic joint (II) New antibiotic treatment for suspected or proven infection of the index joint. (III) Ongoing use of antibiotics for the index joint at the end of follow-up. (IV) Death
Time frame: 15 months after DAIR
Quality of life of patients at baseline and after 6 and 12 weeks
Quality of life, measured with the 5-level EQ-5D version (EQ-5D-5L) questionnaires. The number and percentage of patients reporting each level of problem on each dimension of the EQ-5D-5L will be decribed.
Time frame: at the time of randomization, at week 6 after surgical debridement and after 3 months.
Adverse events
The number of (S)AEs during antimicrobial treatment and follow up (including mortality). ii. The proportion of patients switching to a different oral regimen in both study arms iii. The proportion of patient with antibiotic side effects (classified by the modified Hartwig and Siegel scale) in both study arms iv. The proportion of patient developing Clostridioides difficile infection during treatment in both study arms v. The proportion of patient with rifampicin resistance in bacteria in patients with a microbiologically confirmed failure of treatment in both study arms.
Time frame: through study completion, an average of 15 months
Development of new rifampicin resistance
The proportion of patients developing rifampicin resistance in patients with a confirmed microbiological relapse with the same micro-organism in both study arms
Time frame: through study completion, an average of 15 months
Plan to share: No
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