Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Patients With Peritoneal Dialysis and Peritoneal Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Pharmacokinetics
研究概览
简要总结
Peritoneal infection is still a frequent complication in peritoneal dialysis patients . In France, It contributes to the technique failure, responsible for about 20% of cases of transfer in hemodialysis. The risk of direct mortality is estimated at 1 to 6% according to studies. Peritoneal infection is involved in the dysfunction of the peritoneal membrane.
Based on the recommendations of the International Society for Peritoneal Dialysis, the intraperitoneal route is preferentially recommended. For many antibiotics, pharmacokinetics (intravenous and intraperitoneal) was studied and protocols for IP administration were validated.
Daptomycin, is a cyclic lipopeptide natural, active only on Gram-positive bacteria. It is presented as an alternative to vancomycin in infections resistant pathogens. The stability of daptomycin in peritoneal dialysis fluids (PDF) has been tested, and antimicrobial activity as well.
Seven patients were treated with daptomycin intraperitoneally successfully. But no study has reported pharmacokinetics of daptomycin via the IP route. We propose a pharmacokinetic study of daptomycin administered intraperitoneally in 12 patients on CAPD and with Gram-positive peritoneal infection.
详细描述
Methodology:
Prospective, open-label, non-randomized pharmacokinetic study. Daptomycin will be given IP in the CAPD fluid (200mg in 2L Nutrineal) once daily, in a 6 hours-dwell time. The process of dialysis is done four times per day : three during the day (6,6,and 4 h) and one time at night (8h). Duration of treatment depends on bacteria identified (14 or 21 days).
Analyses will be performed on data from all patients meeting the criteria for inclusion and exclusion.
For each patient, plasma, dialysate and urine kinetics will be studied.
For each parameter, mean and standard deviation are calculated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients > 18 years
- •Hospitalized CAPD patients with Gram positive peritoneal infection : ISPD criterias
- •Presence of two clinical signs and symptoms : abdominal pain, nausea, vomiting, diarrhea, fever and cloudy dialysate
- •Peritoneal dialysate WBC>100/µL with at least 50% polymorphonuclear neutrophil cells
- •Demonstration of bacteria on Gram stain or culture
- •on peritoneal dialysis for at least 3 months
- •written consent, obtained from either the patient, one of his/her relatives, the trusted person who was designated beforehand or, if not possible, emergency enrollment.
- •patient has a life expectancy greater than 6 months
排除标准
- •Known allergy to daptomycin
- •Peritoneal infection with Gram negative only
- •Patient with CPK>5UNL
- •patients already treated with antibiotics, antifungals within 4 weeks prior to the event
- •Patient with hepatic impairment
- •Patient with arguments for an extra-peritoneal site of infection
- •Patient with severe intercurrent illness (eg, hematologic malignancies, patients on chemotherapy)
- •Infection by daptomycin-resistant germ
- •HMGCoA reductase, fibrates or ciclosporin treatment
- •Pregnant or breast-feeding women
研究组 & 干预措施
intraperitoneal daptomycin
3 first patients : 200mg/day 3 following patients : 300mg/day
干预措施: intraperitoneal daptomycin (Drug)
结局指标
主要结局
Pharmacokinetics
时间窗: 14 days
Primary endpoint : Pharmacokinetics study : Evaluation of : * the maximum plasma concentration, * areas under the curve * compartments clearances, * the time during which dialysate concentration is greater than 20mg /L (5xEnterococcus CMI)
次要结局
- tolerance(14 days)