EVRIOS : Comparative Evaluation of Low Versus High Doses of Rifampicin in the Treatment of Staphylococcal Bone and Joint Infections
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 544
- 试验地点
- 16
- 主要终点
- Proven failure
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (over 18 years old) who gave their signed inform consent,
- •Who present an osteo-articular infection with susceptible Staphylococcus spp.,
- •To whom a rifampicin based regimen is prescribed, in association with another antibiotic, for at least 14 days,
- •Patients covered by Health Insurance.
排除标准
- •Patients weighing less than 45 kg or more than 150 kg,
- •Patients with active TB (whatever its localization),
- •Patients needing the imperative use of a treatment presenting a contraindication for concomitant use in the SPC of Rimactan®
- •Patients with a known and documented rifampicin allergy or severe rifampicin intolerance,
- •Patients with galactose intolerance, total lactase deficiency or glucose or galactose malabsorption syndrome, or any other contraindication to the administration of Rimactan® listed in the SPC for Rimactan®
- •Pregnant or breastfeeding woman,
- •Adults legally protected (under judicial protection, guardianship or supervision), persons deprived of their liberty,
- •Patients participating in another interventional clinical trial (biomedical trial or standard care clinical trial).
研究组 & 干预措施
Low dose
Patients will be randomly assigned to low dosage (10 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.
干预措施: Rifampicin (Drug)
High dose
Patients will be randomly assigned to 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.
干预措施: Rifampicin (Drug)
结局指标
主要结局
Proven failure
时间窗: 12 months
The rate of proven failure between the two groups, 12 months after the end of antibiotics. The proven failure is defined as a documented bacteriological failure, with the same Staphylococcus spp. strain isolated before the onset of antibiotics and at diagnosis of failure.
次要结局
- Adverse events(12 weeks)
- Dose modification(12 weeks)
- Possible failure(12 months)
- Failure risk factors(12 months)
- Plasma concentration(12 hours)
- Global health costs(12 weeks)
- Real antibiotics treatment duration(12 weeks)
- Staphylococcus spp. resistance(12 months)