Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Area Under Curve (AUC)
研究概览
简要总结
The purpose of this study is to determine the pharmacokinetics and safety of inhaled vancomycin in patients with cystic fibrosis.
详细描述
The prevalence of methicillin resistant Staphylococcus aureus (MRSA) respiratory infection in patients with cystic fibrosis has increased dramatically over the last decade. Epidemiologic evidence suggests that persistent infection with MRSA may result in an increased rate of decline in FEV1 and shortened survival. Treatment of MRSA is a top priority. Inhaled antibiotics offer the advantage of high concentrations of antibiotic at the site of infection (the airway) while minimizing systemic side effects. Vancomycin is a glycopeptide antibiotic that has activity against MRSA. Anecdotal and retrospective peer-reviewed studies have demonstrated that inhaled vancomycin is safe and potentially effective in patients with cystic fibrosis and MRSA airway infection. Data evaluating the pharmacokinetics of vancomycin in sputum are needed before pursuing treatment trials.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 18 years of age.
- •Confirmed diagnosis of CF based on the following criteria:
- •positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or
- •a genotype with two identifiable mutations consistent with CF or abnormal NPD, and
- •one or more clinical features consistent with the CF phenotype.
- •Chronic sputum producer able to spontaneously produce sputum
- •FEV1 > 40% of predicted normal for age, gender, and height
- •Previous use of any inhaled antibiotics within the last year
- •Ability to provide written informed consent
- •Ability to adhere to the protocol
排除标准
- •Use of inhaled or intravenous vancomycin within two weeks of the study visit
- •Known history of intolerance to inhaled vancomycin or inhaled albuterol.
- •Known history of hypersensitivity to vancomycin or other glycopeptide antibiotics
- •History of sputum culture with Burkholderia cepacia complex in the last two years.
- •Pregnancy
- •Woman who are lactating and not willing to stop nursing on the day of the study visit and the subsequent 48 hours.
- •Current use of oral corticosteroids in doses exceeding the equivalent of 10mg of prednisone a day or 20mg of prednisone every other day.
- •Patients not willing to hold other inhaled antibiotics (for example TOBI, Cayston, or Colistin) for at least 2 days prior to the study visit.
- •Patients not willing to hold loop diuretics (i.e. furosemide, torsemide, ethacrynic acid) on the morning of the study visit.
- •History of ABPA or reactive airways disease that has required treatment within the last year.
- •Creatinine greater than 2.0 mg/dL within the last year.
- •Oxygen saturation ≤ 92% on room air.
- •History of patient reported hearing loss
- •Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or adherence to the protocol.
- •History of or listed for solid organ or hematological transplantation
研究组 & 干预措施
Vancomycin for Inhalation
250 mg vancomycin in 5cc sterile water will be inhaled once. Patients will use a Pari Sprint nebulizer and Pari Vios compressor as the delivery system.
干预措施: Vancomycin (Drug)
结局指标
主要结局
Area Under Curve (AUC)
时间窗: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin
Pharmacokinetic analysis will be performed with non-compartmental methods. The area under the curve for sputum vancomycin will be determined.
次要结局
- Change in Sputum Cell Counts(6 hours)
- Change in FEV1% Predicted(30 minutes)
- Serum Vancomycin Peak Concentration(60 minutes)
- Change in Patient Symptoms(6 hours)
- Oxygen Saturation(5 minutes)
- Adverse Events(6 hours)
- Time to Peak Concentration(Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin)
- Maximum Concentration(Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin)
研究者
Elliott Dasenbrook
Assistant Professor of Medicine and Pediatrics
Case Western Reserve University