The Safety and Pharmacokinetics of Intraperitoneal Administration of Granulocyte-macrophage Colony-stimulating Factor, Fosfomycin, and Metronidazole in Patients Undergoing Appendectomy for Uncomplicated Appendicitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Main trial (14 patients): Drop of white blood cell counts
研究概览
简要总结
The objective of this trial is to evaluate the safety of the intraperitoneal administration of the combination of fosfomycin, metronidazole, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients undergoing surgery for uncomplicated appendicitis. Further, in a sub-trial the aim is to investigate the plasma concentrations of fosfomycin and metronidazole after intraperitoneal administration.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Men ≥18 years old
- •Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual appendectomy
- •Written informed consent after written and verbal information
排除标准
- •Cannot understand, read or speak Danish
- •Previous allergic reaction to fosfomycin, metronidazole, or GM-CSF
- •Perforated appendicitis (diagnosed either during surgery or at a preoperative computer tomography (CT) scan)
- •Diagnostic laparoscopy revealing normal appendix not requiring an appendectomy
- •Other intra-abdominal pathology requiring surgical intervention (diagnosed either during surgery or at a preoperative CT-scan)
- •Known renal or hepatic disease or biochemical evidence at the time of admission
- •Known autoimmune disease or other chronic inflammation
- •Known hematologic disease or cancer
- •Previous abdominal surgery (either laparoscopic or open surgery)
- •Daily use or use of medication one week prior to or during the trial period apart from painkillers such as paracetamol, ibuprofen, tramadol, and morphine as well as drugs needed for anaesthesia, thrombosis prophylaxis, and nausea. Limitations for antibiotics are defined below
- •Use of other antimicrobial agents than the trial treatment one month before until 24 hours after the trial treatment
- •Participant in another drug trial one month prior to the date of the surgery
- •Body mass index ≥35 kg/m2
- •Weekly intake of alcohol >14 units, where one unit corresponds to 12 g alcohol
研究组 & 干预措施
Participants
干预措施: A combination of fosfomycin, metronidazole and GM-CSF i.p. (Drug)
结局指标
主要结局
Main trial (14 patients): Drop of white blood cell counts
时间窗: 4 hours (± 30 minutes)
The safety of intraperitoneal administration is evaluated through the white blood cell counts 4 hours (± 30 minutes) postoperatively. A toxic effect is defined by a drop below the lower reference range.
Sub-trial (8 patients): The pharmacokinetics of fosfomycin.
时间窗: Until 24 hours after surgery ±4 hours.
The plasma concentrations of fosfomycin over time are measured with high-performance liquid chromatography mass spectrometry (HPLC-MS) until 24 hours after surgery ±4 hours.
次要结局
- Main trial (14 patients): Blood pressure(Until 12 hours ±30 minutes.)
- Main trial (14 patients): Frequency of respiration(Until 12 hours ±30 minutes.)
- Main trial (14 patients): Pulse(Until 12 hours ±30 minutes.)
- Main trial (14 patients): Side effects(10 days postoperatively ±1 day.)
- Main trial (14 patients): Adverse events(Until 30 days postoperatively.)
- Main trial (14 patients): Peripheral saturation(Until 12 hours ±30 minutes.)
- Main trial (14 patients): Biochemical markers(4 hours ±30 minutes postoperatively.)
- Main trial (14 patients): Temperature(Until 12 hours ±30 minutes.)
- Main trial (14 patients): Length of stay.(Until 30 days postoperatively.)
- Sub-trial (8 patients): The pharmacokinetics of metronidazole.(Until 24 hours after surgery ±4 hours.)
- Sub-trial (8 patients): Microbiological flora and susceptibility(Until 30 days postoperatively.)
研究者
Siv Fonnes
Principal Investigator
Herlev Hospital