NCT02599493

EVRIOS : Comparative Evaluation of Low Versus High Doses of Rifampicin

EVRIOS : Comparative Evaluation of Low Versus High Doses of Rifampicin in the Treatment of Staphylococcal Bone and Joint Infections

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 544 (actual)
• Sponsor: Rennes University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Rifampicin is an antibiotic usually required to treat susceptible Staphylococcus spp. osteo-articular infections, most frequently in association with a fluoroquinolone when the strain is susceptible to both agents. It is the reference treatment for orthopedic infections with implanted material. For tuberculosis treatment the dosage of 10 mg/kg/j is usually prescribed, while in the treatment of Staphylococcus spp. infections the highest dosage of 20 mg/kg/j is proposed by French experts' recommendations from 2009. However, there is little evidence in the literature, which could set out arguments to choose the best dosage of rifampicin, which may vary from 5 to 20 mg/kg. The issue with rifampicin is side effects, in particular with long-term treatment. Many side effects may occur in 10 to 20% of patients and sometimes leads to dosage reduction or treatment interruption. In the literature, there is little evidence that higher rifampicin dosage is associated with higher frequency of adverse effects. Depending on the nature of the toxicity, one could say that hypersensitivity could be independent from dosage, when digestive disorders may be related. Plasmatic concentrations studies have not given strong arguments to link higher rifampicin dosages with side effects occurrence rates. After oral absorption, plasmatic peak occurs after two to five hours and varies among individuals but also in the same patient overtime. This particular pharmacokinetic profile could explain discrepancy in adverse events (AEs) frequencies.

Detailed description

Primary objective : To demonstrate that a daily weight-based low dose of rifampicin is non-inferior to a high dose in the treatment of susceptible Staphylococcus spp. osteo-articular infections. Secondary objectives : To compare, in the two treatment groups (weight-based low dose rifampicin versus weight-based high dose): * Possible failure rates (when no bacteriological samples are available or when clinical manifestations are not straightforward), * AEs distribution: * Those self-patient reported, * Those medical or biological reported, * \- Rifampicin dose modifications: * Dosage decrease, * Treatment interruption (temporary or definitive), * Failure risk factors analysis, * Health costs related to the osteo-articular infection care: number and length of hospitalizations, number of follow-up visits, nature and number of all biological samples prescribed in both groups. * Comparison of the planned rifampicin exposure in each randomization group * Differences in rifampicin duration (planned versus effective duration) according to allocated group, * Rifampicin pharmacokinetics sub-study in a small sample of 60 patients, * Rifampicin resistance bacteriological study in patients with proven failure. Methodology : Non-inferiority prospective, multicentre, randomized, open-label, controlled phase IV trial evaluating two different rifampicin dosages (high versus low dose) in the treatment of staphylococcal bone and joint infections. Treatment : Patients will be randomly assigned to low dosage (10 mg/kg/j) rifampicin group or high dosage (20 mg/kg/j) rifampicin group. Rifampicin treatment will be prescribed in association with another antibiotic chosen by investigator according to the antibiogram results. Association with fluoroquinolones is the first choice combination, if it is possible. The global antibiotic treatment duration depends on the investigator's choice.

Conditions

• Osteoarticular Infection

Interventions

Type	Name	Description
DRUG	Rifampicin	Patients will be randomly assigned to low dosage (10 mg/kg/j) rifampicin group or high dosage (20 mg/kg/j) rifampicin group. Rifampicin treatment will be prescribed in association with another antibiotic chosen by investigator according to the antibiogram results. Association with fluoroquinolones is the first choice combination, if it is possible. The global antibiotic treatment duration depends on the investigator's choice.

Timeline

• Start date: 2016-01-01
• Primary completion: 2020-12-01
• Completion: 2020-12-01
• First posted: 2015-11-06
• Last updated: 2021-08-23

Locations

16 sites across 1 country: France