Rifabutin Versus Rifampicin for Treatment of Staphylococcal PJI Treated With DAIR
ConditionProsthetic Infection
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorTourcoing Hospital
About this trial
Rifampicin, is key in the treatment of staphylococcal PJIs. Rifabutin has a better profile of tolerance than rifampicin regarding the risk of interaction with concomitant medications and liver disorders. The hypothesis is that rifabutin may be an alternative antibiotic option as efficient as rifampicin for the treatment of staphylococcal PJIs, with a better safety profile. The investigator aim to demonstrate the non-inferiority of rifabutin as compared with rifampicin prescribed in combination treatment for PJIs.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Hip or knee Prosthetic joint infection treated by debridement, antibiotic therapy initiation and retention of prothesis (DAIR strategy)
Staphylococcus aureus
Coagulase-negative staphylococci
Microorganisms susceptible to rifampicin and at least one other antibiotic suitable for the treatment of PJI (e.g., penicillin, fluoroquinolone, (doxy/mino)cycline, oxazolidinone, cotrimoxazole, daptomycin, glycopeptide, macrolide, fusidic acid), regardless of sensitivity to methicillin.
Disqualifiers
Suspicion of reduce absorption of oral treatment due to abdominal disorder Known or suspected malabsorption (imperfect absorption of food material by the small intestine)
Polymicrobial infection due to other than staphylococcus species susceptible to rifampicin
Known or suspected allergy to rifabutin and/or rifampicin
Diagnosis of endocarditis associated to PJI
Trial design
Design model
Parallel
Treatments tested in this trial
Rifabutin
Drug2 tablets of 150 mg per day rifabutin tablet daily for 12 weeks in 1 administration with a companion treatment
Rifampicin
Drug10 mg/kg per day (range 600 mg to 1,200 mg) rifampicin tablet in 1 daily dose for 12 weeks with a companion treatment
Treatment groups
436 Participants
are divided into 2 treatment groupsGroup A: RIFAMPICINActive comparator 1 intervention
Group B: RIFABUTINExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Treatment failure
Treatment failure defined as one of following events: * The need for any further surgical procedure - i.e. implants removal, implants exchange or amputation; * And/or PJI related death; * And/or use of suppressive antibiotic therapy that was not planned before randomization
Time frame
At one yearSecondary outcomes
1
Occurrence of serious adverse events (SAEs), including death (i.e. all cause)
Proportion of patient which are free from SAEs occurrence, as defined by: -Patients who completed the entire 12 weeks duration of antibiotic treatment planned initially and; xWho did not experience grade 3-4 adverse events, including death, regardless of the link with antibiotic therapy; xWho did not experience adverse events which led to either to: * Reduce the dosage or split the treatment to two take/day; * Or stop any component of the antibiotic treatment.
Time frame
At the end of 12 weeks duration of antibiotic treatment planned2
Occurrence of any adverse event that could be related to rifampicin or rifabutin
Number and rate of patients in each arm who experiences: * Liver cytolysis (\>=2N for ALT AND/OR AST) * Acute Kidney failure as defined by serum creatinine increase in KDIGO * Digestive symptoms, including diarrhea * Who required a modification of antibiotic dosage during the 12 weeks' period of antibiotic treatment * Uveitis/ophthalmologic disorder * Neurological disorder
Time frame
At the end of 12 weeks duration of antibiotic treatment planned3
Proportion of patients from each arm who will complete the 12-week duration of rifampicin/rifabutin treatment, early termination of the planned 12 weeks' period of antibiotics
Early termination rate will be measured in each arm, as the number of patients having stopped rifampicin or rifabutin before the planned 12 weeks period over the total number of patients enrolled in the studied arm.
Time frame
At the end of 12 weeks duration of antibiotic treatment planned4
Adherence to antibiotics regimen
Adherence rate to medication will be measured as the number of days on which all doses were missed over the number of days of planned antibiotic therapy. Patients enrolled in the study will have to fill their pill count in a daily notebook.
Time frame
At the end of 12 weeks duration of antibiotic treatment plannedSponsors and contacts
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Source ClinicalTrials.gov