Aztreonam Aerosol to Treat Cystic Fibrosis Nasal Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140
研究概览
简要总结
This study is designed as a masked, two center, randomized, placebo-controlled pilot study to evaluate the safety and efficacy of nasal and oral inhalation of 75 mg aztreonam in subjects with CF and lung infection due to PA. The study will involve two sites: Virginia Commonwealth University Medical Center (VCU) and Eastern Virginia Medical School (EVMS). Potential subjects will be identified in each site's CF clinic.
详细描述
This study is designed to explore the efficacy and safety of nasal aztreonam administered using the Pari Sinus Nebulizer combined with oral Cayston aerosol therapy compared to placebo on clinical and laboratory endpoints such as risk of antibiotic-resistant Pseudomonas aeruginosa (PA), time to pulmonary infection exacerbation, nasal quality of life, pulmonary function, nasal and lower airway cultures, and properties of mucus.
P. aeruginosa (PA) is a primary cause of lung infections in persons with cystic fibrosis (CF) (1). Over the past decade, studies have shown that aerosolized antibiotics can reduce lower respiratory bacterial load, decrease exacerbations of pulmonary disease, and in many patients improve pulmonary function. Cayston (aztreonam) oral aerosol using the PARI Altera Nebulizer System was approved by the FDA in February 2010 for CF patients 7 years of age or older with PA (2). In 2011, 35.8% or patients in the National CF Patient Registry used Cayston for treatment (3). Bacterial cultures suggest that the upper airways and lower airways of CF patients are cross-infected by PA and that the paranasal sinuses can act as a bacterial reservoir (4). There is improved post-transplanation patient survival for recipients that undergo sinus surgery and daily nasal washes to reduce bacterial load (2).
Routine CF care does not generally include upper airway assessment. There are no published studies evaluating the effect of aerosol antibiotics to treat nasal and sinus infections in CF in combination with oral inhaled aerosol therapy to treat the lower airway disease. However Mainz and colleagues published a case report that suggested that sinonasal administration of tobramycin using the Pari Sinus nebulizer (Pari Corp, Starnberg, Germany) delayed PA lower respiratory infection in a 12 year-old with CF who had chronic mucopurulent rhinosinusitis (5) and studies in chronic obstructive pulmonary disease suggest that treating upper airways can also improve coexistent lower airway disease.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 7 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females 7 years of age or older and able to perform pulmonary function testing
- •Confirmed diagnosis of CF by the 1997 CF Consensus Conference criteria and followed by the VCU or EVMS CF clinic
- •Presence of PA in 2 lower respiratory tract (sputum) cultures in the 24 months before screening
- •Subjects and/or parent guardian must be able to give written informed consent prior to any study related procedure
- •All sexually active female subjects who are of childbearing potential must agree to use an effective method of contraception (i.e.condoms or abstinence).
- •All sexually active female subjects must have a negative pregnancy test at screening (V0).
- •Clinically stable determined by the study physician with no significant new respiratory symptoms.
- •Presence of PA in nasal culture (swab or secretion) or sinus culture obtained in the 12 months before screening or at screening visit
排除标准
- •Use of oral, IV or inhaled antibiotics within 0 days before study other than low dose azithromycin
- •Severe pulmonary disease with FEV1<30% predicted of baseline SpO2<0.90
- •ENT surgery within 6 months of screening
- •Allergy or documented adverse reaction to aztreonam
- •Epistaxis or significant (>30mL) hemoptysis in the past 6 months
- •Frequent (weekly or more frequently) or severe headaches
- •Subject is unlikely to comply with the procedures scheduled in the protocol
- •Subject participates in another clinical trial within 30 days prior to study entry
- •Subjects who have had a lung transplant will be excluded
- •Prisoners will be excluded
- •Non-English Speaking patients will be excluded
研究组 & 干预措施
Standard Therapy
Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day
干预措施: Oral Aztreonam (Drug)
Standard Therapy
Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Nasal Placebo-Normal Saline twice per day
干预措施: Nasal Placebo (Drug)
Study Therapy
Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day
干预措施: Oral Aztreonam (Drug)
Study Therapy
Oral Inhalation via PARI Altera Device: Standard Therapy Comparator (Oral Aztreonam 75mg three times a day) AND Nasal Inhalation via PARI PAS Device: Experimental- Nasal Aztreonam 75 mg twice per day
干预措施: Nasal Aztreonam (Drug)
结局指标
主要结局
Number of Protocol-defined Pulmonary Exacerbations Treated With IV Anti-pseudomonal Antibiotics on Day 140
时间窗: 140 days
Protocol-Defined Pulmonary Exacerbation includes events that are characterized by change or worsening pulmonary symptoms (increased cough, increased sputum production and chest congestion, decreased appetite and exercise tolerance), loss of weight, and lung function decline that prompt initation of antibiotic therapy. Protocol-defined exacerbations in subjects that warrant treatment with IV antibiotics will be determined from the medical record during the course of this study.
次要结局
- Change in Sinus and Nasal QoL Questionnaire (SNOT-20) on Day 140 and Day 168(Day 140 and Day 168)
- Change in Paired Sputum Cultures and Nasal Swabs for Bacteria and Antibiotic Resistance(1 year)
- Change in Pulmonary Function (FVC and FEV1 Percent Predicted) on Day 140(Day 140)
- Change in Cystic Fibrosis QoL Score (CFQ-R) on Day 140(Day 140)
- Change in Acoustic Rhinometry for Nasal Obstruction (Volume) (Will be Measured at VCU Site ).(1 year)
- Number of Protocol-defined Pulmonary Exacerbations Treated With Oral Anti-pseudomonal Antibiotics(1 year)
- Time to First Protocol-defined Pulmonary Exacerbation Treated With IV Anti-pseudomonal Antibiotics(Up to 6 months)
- Number of Safety and Adverse Events Including Nasal Stuffiness, Epistaxis, and Headache.(1 year)