Randomized Double Blind Controlled Trial of the Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy in Chronic Pseudomonas Aeruginosa Infected Cystic Fibrosis Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 5
- 主要终点
- The proportion of patients in the intervention arm versus the control arm who have ≥ 3 log drop in colony forming units (CFUs) of P. aeruginosa in sputum.
研究概览
简要总结
The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. aeruginosa infection with an acute pulmonary exacerbation is a safe intervention that will result in improved microbiological and clinical outcomes and decrease markers of pulmonary inflammation.
详细描述
Cystic fibrosis (CF) is the most common fatal genetic condition in the Caucasian population and affects over 3,000 Canadians. Respiratory failure caused by chronic pulmonary infection is the primary cause of death in CF patients. The improved life expectancy of CF patients in the past several decades is due in part to the more aggressive use of antibiotics in the treatment of respiratory infections. However, there is currently no antimicrobial susceptibility assay that can predict which antibiotics will result in improved patient outcomes. Since Pseudomonas aeruginosa is known to grow as a resistant biofilm in the CF lung, antimicrobial susceptibility testing based on biofilm growth of P. aeruginosa may lead to different antibiotic choices that significantly decrease the pulmonary bacterial density of P. aeruginosa. A biofilm antimicrobial susceptibility assay thus has the ability to change the way antibiotics are chosen to treat CF patients and result in improved lung function and longer lives for all CF patients.
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
- Double (Participant, Investigator)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CF based on the following: sweat chloride > 60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF
- •Chronically infected with P. aeruginosa (>50% of respiratory specimens positive for P. aeruginosa in the 24 months prior to screening)
- •Able to produce sputum (expectorated or induced)
- •Able to reproducibility perform pulmonary function testing
- •Written informed consent provided
排除标准
- •Sputum culture negative for P. aeruginosa or with a density of less that 10^5 CFU/g at screening
- •Sputum culture positive for Burkholderia cepacia at screening
- •History of B. cepacia positive respiratory culture within 24 months prior to screening
- •Use of antibiotics other than those prescribed by the principal investigator
- •History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option
- •History of anaphylaxis or other life threatening complication to any antibiotic in the six groups that are a therapeutic option
- •Post lung transplantation or listed for lung transplantation
- •Pregnancy
- •A septic or clinically unstable patient
- •Presence of a condition or abnormality that in the opinion of an investigator would compromise the safety of the patient or the quality of the data
研究组 & 干预措施
Control Arm
干预措施: Conventional antimicrobial susceptibility testing (Other)
Intervention Arm
干预措施: Biofilm antimicrobial susceptibility testing (Other)
结局指标
主要结局
The proportion of patients in the intervention arm versus the control arm who have ≥ 3 log drop in colony forming units (CFUs) of P. aeruginosa in sputum.
时间窗: Measured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
次要结局
- The change in pulmonary function tests, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal midexpiratory flow rate (FEF25-75) in the intervention arm versus the control arm(Measured at day 0, day 7, and day 14 of antibiotic treatment and at the 1 month follow-up visit)
- The time to subsequent acute pulmonary exacerbation in the intervention arm versus the control arm(1 year following the completion of antibiotic therapy)
- The change in the cumulative score on a quality of life questionnaire in the intervention arm versus the control arm(Measued at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit)
- The change in the measurement of markers of pulmonary inflammation (neutrophil counts, neutrophil elastase and IL-8 levels in sputum) in the intervention arm versus the control arm.(Meaured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit)
研究者
Valerie Waters
Staff Physician
The Hospital for Sick Children